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IMEG SEMINARS
Fall 2005
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| Previous IMEG
Seminars and Abstracts: |
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|
| Date |
Speaker
and title of seminar |
08/31/05 |
NO
CLASS |
|
| 09/07/05 |
Speaker: Dr. Horoshi Akashi - Department of
Biology
Title: Molecular evolution in the Drosophila
melanogaster species subgroup:
Frequent parameter
fluctuations on the time-scale of molecular divergence
Abstract: Although mutation, genetic
drift, and natural selection are well-established as determinants of
genome evolution, the importance (frequency and magnitude) of
parameter fluctuations in molecular evolution is less
understood. DNA sequence comparisons among closely related
species allow specific substitutions to be assigned to lineages on a
phylogenetic tree. In this study, we compare patterns of codon
usage and protein evolution in 22 genes (>11,000 codons) among
Drosophila melanogaster and five relatives within the D.
melanogaster subgroup. We employ a maximum likelihood
approach to infer ancestral states and assign changes to eight
lineages. Four of the eight lineages show potentially
genome-wide departures from equilibrium synonymous codon usage;
three are decreasing and one is increasing in major codon
usage. Several of these departures are consistent with
lineage-specific changes in selection intensity (selection
coefficients scaled to effective population size) at silent
sites. Intron base composition and rates and patterns of
protein evolution are also heterogeneous among these lineages.
The magnitude of forces governing silent, intron, and protein
evolution appear to have varied frequently, and in a
lineage-specific manner, within the D. melanogaster subgroup.
Establishing the mechanisms underlying these patterns will be
critical for interpreting tests of adaptive protein evolution that
rely on contrasts between silent and replacement changes.
References:
Ko, W.Y., R. David, and H. Akashi, 2003
Molecular phylogeny of the Drosophila melanogaster species
subgroup. Journal of Molecular Evolution 57: 562-573.
Akashi, H., 2001 Gene expression and molecular
evolution. Current Opinions in Genetics and Development 11:
660-666.
Akashi, H. 1995 Inferring weak selection from
patterns of polymorphism and divergence at "silent" sites in
Drosophila DNA. Genetics 139: 1067-1076. |
|
| 09/14/05 |
Speaker: Dr. Will Provine - Cornell
University
Title: Random genetic drift: A reassessment in
historical perspective
Abstract: Provine will first argue
that the "evolutionary synthesis" is a poor guide in modern
evolutionary biology, and then address Sewall Wright's use of the
concept of random genetic drift in his view of the evolutionary
process. Wright always saw random drift and inbreeding as basically
the same thing. Provine will attempt to distinguish random genetic
drift from inbreeding, founder effects, and small effective
population size. An assessment follows of the foundation studies of
random drift in the mid-1950s by Wright and Kerr, Kerr and Wright,
Buri, Crow and Morton, and Dobzhansky and Pavlovsky.
The
second half of the talk is devoted to the role of random drift in
deep evolutionary time, namely in the theories of neutral molecular
evolution. Provine will argue that summarizing the neutral theories
as the "neutral mutation-random drift hypothesis" is
inadequate. Neutral molecular evolution remains the most
surprising, important, and robust development in evolutionary
biology since the "evolutionary synthesis," whether or not movement
of selectively neutral mutations is determined by random drift,
hitchhiking, or other means of movement. |
|
| 09/21/05 |
Speaker: Dr. Yoshihito Niimura - Tokyo
Medical and Dental University, Tokyo, Japan
Title: Evolutionary Dynamics of
Vertebrate Olfactory Receptor Genes
Abstract: Vertebrates can
discriminate among thousands of different odor molecules in the
environment. Odor molecules are detected by olfactory receptors
(ORs), which form the largest known multigene family in vertebrates.
To understand the evolutionary dynamics of OR genes, we have
conducted a phylogenetic analysis of all functional genes identified
from the genome sequences of zebrafish, pufferfish, frogs, chickens,
humans, and mice. The results suggested that the most recent common
ancestor between fishes and tetrapods had at least nine ancestral OR
genes, and all OR genes identified were classified into nine groups
each of which originated from one ancestral gene. Eight out of the
nine group genes are still observed in current fish species, while
only two group (a and g) genes were found from mammalian or avian
genomes with a few exceptions. In mammals or birds, group g genes
expanded enormously, containing ~90% of the entire gene family.
Group a and g genes are nearly absent in fishes, while four major
group genes present in fishes are completely absent in mammals or
birds. The expansion of group g genes has also occurred in frogs,
but frogs retain the group genes that are abundant in fishes,
indicating that the frog OR gene family has both mammal-like and
fish-like characters. These observations can be explained by the
environmental change that organisms have experienced after the
divergence between fishes and tetrapods. In the tetrapod lineage,
repeated gene duplications and massive gene losses appear to have
occurred to adapt in the terrestrial environment, whereas the change
in OR gene repertoire in the fish lineage seems smaller than that in
the tetrapod lineage, reflecting a smaller environmental change from
the common ancestor.
References:
Niimura, Y. and Nei,
M. (2003) Evolution of olfactory receptor genes in the human genome.
Proc. Natl. Acad. Sci. USA 100:
12235–12240.
Niimura, Y. and Nei,
M. (2005) Comparative evolutionary analysis of olfactory receptor
gene clusters between humans and mice. Gene
346:
13–21.
Niimura, Y. and
Nei, M. (2005) Evolutionary dynamics of olfactory
receptor genes in fishes and tetrapods. Proc. Natl. Acad. Sci.
USA 102: 6039–6044. |
|
| 09/28/05 |
Speaker: Li Hao - Department of
Biology
Title: Comparative genomics and evolutionary
analysis of natural kill cell receptor gene
complex
Abstract: The natural killer (NK) receptor
gene complex (NKC) encodes a large number of C-type lectin receptors
which are expressed on NK cells and other immune-related cells.
These lectin-type NK cell receptors play an important function in
regulating NK-cell cytolytic activity and subsequently protect cells
against virus infection and tumorigenesis. To understand
evolutionary dynamics of these lectin genes in NKC, we characterized
the entire NKC gene structures from humans, mice, rats, and dogs and
then conducted phylogenetic analysis of all putative functional
genes. Results show that the number of genes in NKC of rodents is
twice more than that of humans and dogs, which is mainly due to
rodent-specific expansion of certain gene families, including Klra
and Ocil, etc. The entire NKC can be divided into 4 smaller genomic
clusters (A~D). The birth-and-death rates of the gene families among
different genomic clusters are different, in which the cluster C
contains more or less the similar number of genes among species,
whereas the cluster B and D show a trend of rodent-specific
expansion. To investigate the origin of these NKC genes, we also
searched the putative NKC sequences from cattle, opossum, and
chicken genomes. The results indicate that the expansion of the NKC
gene families might have occurred before the separation of placental
and marsupial mammals but after the divergence between birds and
mammals.
References:
Kelley, J., L. Walter, and
Trowsdale. 2005. Comparative genomics of natural killer cell
receptor gene clusters. PLoS Genetics
1:129-139. |
|
| 10/05/05 |
Speaker: Dr. Eddie Holmes - Department of
Biology
Title: The Evolutionary Genetics of RNA
viruses
Abstract: RNA viruses are of great biological
importance because of their role as agents of disease. Herein
I will discuss the mechanisms of evolution in RNA viruses in general
and then explore how they relate to one important emerging pathogen
in particular. I will begin by examining the key mechanisms of
evolution in RNA viruses; mutation (especially the frequency of
deleterious mutation), natural selection (including epistasis and
immunodynamics), recombination (including reassortment and true RNA
recombination) and population size (particularly population
bottlenecks at transmission). I will argue that the rate of
deleterious mutation is so great that it acts as a major adaptive
constraint and that this may have a major effect on emergibiility,
although long-term population sizes may be sufficiently large to
avoid fitness losses. I will then discuss the evolutionary
genetics of dengue virus (DENV) in particular. By examining
the evolution of DENV in a variety of epidemiological contexts I
will show that deleterious mutations are also commonplace in this
virus and may survive in the long-term by a process of
complementation. I will also argue that complex
immunodynamics, caused by the co-circulation of multiple serotypes
within populations, may also exert a major selective force on this
virus.
References:
Moya A,
Holmes EC & González-Candelas F. (2004). The population genetics
and evolutionary epidemiology of RNA viruses.
Nat.Rev.Microbiol. 2,
279-287.
Holmes EC & Twiddy
SS. (2003). The origin, emergence and evolutionary genetics of
dengue virus. Infect.Genet.Evol. 3,
19-28. |
|
| 10/12/05 |
Speaker: Wen-Ya Ko - Department of Biology
Title: Extreme region-specific
heterogeneity in base composition evolution on the Drosophila X
chromosome.
Abstract: Fluctuations in base
composition have been noted in Drosophila and mammal genomes
evolution, but their frequency and genomic breadth, as well as their
causes, remain obscure. Here, we investigated evolution of
base composition from fourteen genes located at the telomeric region
and nine genes from the non-telomeric regions of X chromosome among
Drosophila melanogaster and five of its close
relatives. Substitutions were inferred on each of eight
lineages by a maximum likelihood method. Comparative studies
between the two chromosomal regions revealed striking
heterogeneities in base composition evolution at the telomeric
region in D. yakuba and D. orena. While
AT-increasing synonymous changes were shown in the non-telomeric
loci, opposite patterns were found in the telomeric genes in both
lineages. The genomic breadths and magnitudes of changes also
differ between these two lineages. At the telomeric region,
loci that show GC-increasing synonymous changes cover a region as
large as approximately 1.2 Mb in D. yakuba, but
restrict to a much smaller region, approximately 0.13 Mb, in D.
orena. Numbers of AT->GC changes at this small region
in D. orena are striking, about 15 folds higher than the
numbers of GC->AT changes. Comparisons of nucleotide
substitution patterns between coding and adjacent intronic regions
shed some light on the evolutionary mechanisms underlying these
patterns. The GC-increasing patterns of synonymous changes in
D. yakuba are less consistent with fluctuations in mutational
processes. On the other hand, neutral mechanism appears to
have significant contributions to the GC-increasing patterns found
in D. orena. However, larger magnitudes of
GC-increasing silent changes within the coding regions than within
the intronic regions suggest contributions of natural selection or
biased gene conversion.
References:
Akashi, H. 1996. Molecular
evolution between Drosophila melanogaster and D.
simulans: reduced codon bias, faster rates of amino acid
substitution, and larger proteins in D. melanogaster. Genetics
144:1297-1307.
Takano-Shimizu, T. 1999. Local
recombination and mutation effects on molecular evolution in
Drosophila. Genetics 153:1285-1296.
Takano-Shimizu, T. 2001. Local
changes in GC/AT substitution biases and in crossover frequencies on
Drosophila chromosomes. Mol Biol Evol
18:606-619. |
|
| 10/19/05 |
Speaker: Chiao-Feng Lin - Department of Biology
Cancelled
Title:
Abstract:
References: |
|
| 10/26/05 |
Speaker: Wen-Yu Chung - Department of Computer Science
and Engineering
Title: Rapid
and Asymmetric Divergence of Duplicate Genes in the Human Gene
Coexpression Network
Abstract: Motivation: While gene duplication is known to be one of the
most common mechanisms of genome evolution, the fates of genes after
duplication are still being debated. In particular, it is presently
unknown whether most duplicate genes preserve (or subdivide) the
functions of the parental gene or acquire new functions. One aspect
of gene function, that is the expression profile in
gene
coexpression network, has been largely unexplored for
duplicate genes. Results: Here we build a human gene coexpression
network using human tissue-specific microarray data and investigate
the divergence of duplicate genes in it. The topology of this
network is scale-free. Interestingly, our analysis indicates that
duplicate genes rapidly lose shared coexpressed partners: after
approximately 50 million years since duplication, the two duplicate
genes in a pair have only slightly higher number of shared partners
as compared with two random singletons. We also show that duplicate
gene pairs quickly acquire new coexpressed partners: the average
number of partners for a duplicate gene pair is significantly
greater than that for a singleton (the latter number can be used as
a proxy of the number of partners for a parental singleton gene
before duplication). The divergence in gene expression between two
duplicates in a pair occurs asymmetrically: one gene usually has
more partners than the other one. The network is resilient to both
random and degree-based in silico removal of either singletons or
duplicate genes. In contrast, the network is especially vulnerable
to the removal of highly connected genes when duplicate genes and
singletons are considered together. Thus, duplicate genes rapidly
diverge in their coexpression profiles in the network and play
similar role in maintaining the network robustness as compared with
singletons. References:
Albert, R. and A.L. Barabasi. 2002.
Statistical mechanics of complex networks.
Reviews of Modern
Physics 74:47-96
Makova, K.D. and W.H. Li. 2003. Divergence in
the spatial pattern of gene
expression between human duplicate
genes. Genome Res 13:1638-1645
Wagner, A. 2005. Distributed
robustness versus redundancy as causes of
mutational robustness.
Bioessays 27:176-188 |
|
| 11/02/05 |
Speaker: Chiao-Feng Lin - Department of
Biology
Title: Evolution of Minor (U12) Type of Introns
Abstract:
Two analogous pathways (U2- and
U12-dependent) for the splicing of pre-mRNAs are found in many
higher eukaryotes, including human, mouse, fruit fly and /Arabidopsis/. But the U12-dependent pathway seems
to be missing in yeast and nematode. The minor type of intron is
referred to as U12 because these introns are rare and are removed by
a much less abundant splicing complex containing U12 rather than U2
snRNA. U12 introns possess two highly conserved motifs (5’ Splice
Site and Branch Point Site) that allow us to determine, in silico,
whether an intron is of the U12-type or U2-type. It is proposed that
very stringent requirement of 5’SS and BPS signals made U12 introns
much more susceptible to mutations. Disruption of splicing signals
may convert a U12 intron to a U2 intron, while conversion of a U2
intron to a U12 intron is much less likely. Thus, U12-introns tend
to be lost from a genome (1). Two genome-wide studies - in human (2)
and /Arabidopsis/ (3) - showed that frequencies of U12
introns are significantly different in the two species. However,
variation in the frequency of U12 introns among lineages has never
been investigated. In this study, using a comparative genomics and
phylogenetic approach, we scanned seven complete genomes (/Arabidopsis/, rice, human, mouse, rat, pufferfish,
and fruit fly) for U12 introns. Phylogenetic analysis of
U12-containing genes enabled us to identify patterns of evolutionary
conservation of U12 introns.
References:
1. Burge CB, Padgett RA, Sharp PA 1998.
Evolutionary fates and origins of U12-type introns. /Mol Cell/ 1998 Dec; 2(6):773-85
2. Levine,
A. and R. Durbin (2001). A computational scan for U12-dependent
introns in the human genome sequence. /Nucl. Acids Res/ 29(19): 4006-4013.
3. Zhu, W. and
V. Brendel 2003. Identification, characterization and molecular
phylogeny of U12-dependent introns in the Arabidopsis thaliana
genome. /Nucl.
Acids. Res/ 31(15):
4561-4572. |
|
| 11/09/05 |
Speaker: Zhenguo Lin - Department of
Biology
Title: Phylogenetic Analyses of RecA/RAD51-like Gene
Family
Abstract: DNA repair and homologous recombination are critical for cell
viability, genome stability and creating genetic diversity.
Recombinase RecA/RAD51 family proteins have been found in all
cellular organisms and play critical rules in DNA repair and
homologous recombination. Multiple members of RecA/RAD51 family have
been identified in Archaea (RADA, RADB) and Eukaryota (RAD51,
RAD51B, RAD51C, RAD51D, DMC1, XRCC3 and XRCC2, RecA). We performed
extensive phylogenetic analyses using RecA/RAD51-like protein
sequences and proposed a hypothesis about evolutionary relationships
of RecA/RAD51 gene family. Our results demonstrate that all the
members of eukaryotic RAD51 like genes were diverged from a common
ancestor by ancient gene duplication events. The first gene
duplication event occurred before divergence of Archaea and
Eukaryota to producing two major subfamilies: Type A including
RAD51, DMC1, RADA and Type B including RADB, RAD51C, RAD51B, RAD51D,
XRCC2 and XRCC3. Type A proteins play central roles in DNA repair
and homologous recombination while Type B proteins, which form
different complexes, play supporting rules of RAD51/DMC1 and develop
other functions in other processes. Multiple bacteria RecA like
genes found in eukaryotic genomes were probably originated from
eubacterial endosymbionts by horizontal gene transfer through the
endosymbiosis events of chloroplasts and mitochondria.
References:
Thacker, J. (1999). "A surfeit of
RAD51-like genes?" Trends Genet 15(5):
166-8.
Bleuyard, J. Y., M. E. Gallego, et al. (2005). "Differing
requirements for the Arabidopsis Rad51 paralogs in meiosis and DNA
repair." Plant J 41(4): 533-45.
Masson, J. Y., M.
C. Tarsounas, et al. (2001). "Identification and purification of two
distinct complexes containing the five RAD51 paralogs." Genes
Dev 15(24): 3296-307.
|
|
| 11/16/05 |
Speaker: Dr. Zhi-Chun Lai - Department of
Biology
Title: Growth Inhibition and Tumor Suppression by a Mob Family
Protein, Mats"
Abstract: We have discovered a novel
tumor suppressor, Mats, which determines cell number and tissue
growth through restricting cell proliferation and promoting
apoptosis in Drosophila. Our genetic and biochemical
studies revealed that Mats functions as an activating subunit of
another tumor suppressor, Wts protein kinase. Mats orthologs
exist in plants and animals, and Mats-mediated growth inhibition is
likely conserved in humans. Moreover, we have evidence to show
that Mats is a key component of Hippo growth inhibitory and tumor
suppression pathway. Thus, this work extends our understanding
of tissue growth and cell number control during development and
tumorigenesis, and raises the possibility that Mats-dependent growth
inhibition and tumor suppression may have important implications for
the understanding and treatment of human cancers.
References:
Lai, Z.-C. Wei, X.,
Shimizu, T., Ramos, E., Rohrbaugh, M., Nikolaidis, N., Ho, L.-L.,
and Li, Y. (2005). Control of cell proliferation and apoptosis by
Mob as tumor suppressor, Mats. Cell 120:
675-685. |
|
| 11/23/05 |
No Classes - THANKSGIVING
HOLIDAY |
|
| 11/30/05 |
Speaker: Dr. Teh-hui Kao - Department of Biochemistry
and Molecular Biology
Title: S-RNase-Based
Self-Incompatibility in Flowering Plants
Abstract: Self-incompatibility (SI) is
an intraspecific reproductive barrier that allows the pistil of many
flowering plants to distinguish between self- and non-self
pollen. Self-pollen is rejected whereas non-self pollen is
accepted for fertilization. It is estimated that more than
half of the flowering plant species, representing more than 60
families, possess SI. To date, three different SI mechanisms
have been identified from studies of five of the families, and the
S-RNase-based SI mechanism is possessed by three of them: the
Solanaceae (containing petunia, potato, tobacco, tomato)
Scrophulariaceae (containing snap dragon) and Rosaceae (containing
almond, apple, cherry). Here, the highly polymorphic
S-locus controls the specificity of SI interactions between
pollen and the pistil. If pollen carries an S-haplotype
that matches one of the two S-haplotypes of the pistil, it is
recognized as self-pollen and the growth of its tube is inhibited in
the style. The S-locus contains two separate genes: the
S-RNase gene, identified in the late 1980s, controls pistil
specificity, and the recently identified S-locus F-box
(SLF) gene controls pollen specificity. In this talk, I
will focus on our use of Petunia inflata as a model to study
the mechanism of S-RNase-based SI. I will describe how the
S-RNase gene and the SLF gene were identified,
properties of S-RNase and SLF, and our ongoing effort to study how
S-RNase and SLF mediate growth inhibition of self-pollen tubes.
References:
Wang Y, Wang X, McCubbin AG,
Kao T-h (2003). Genetic mapping and
molecular characterization of the self-incompatibility (S-)
locus in Petunia inflata. Plant Mol Biol 53: 565-580
Kao T-h,
Tsukamoto, T (2004). The molecular and genetic bases of
S-RNase-based self-incompatibility. Plant Cell 16: S72-83
Sijacic P, Wang X, Skirpan AL, Wang Y, Dowd PE, McCubbin AG, Huang
S, Kao T-h (2004). Identification of the pollen determinant of
S-RNase-mediated self-incompatibility. Nature 429: 302-305
Wang Y, Tsukamoto T, Yi K-w, Wang X, Huang S, McCubbin AG, Kao T-h
(2004). Chromosome walking in the Petunia inflata
self-incompatibility (S-) locus and gene identification in an
881-kb contig containing S2-RNase. Plant Mol
Biol 54: 727-742
|
|
| 12/07/05 |
Speaker: Fabia Battistuzzi - Department of
Biology
Title: Eukaryote-prokaryote relationships and the origin of
eukaryotes
Abstract: Multiple hypotheses have been proposed in past years for the
origin of eukaryotes. Of these the one that has received more
evidence and consensus is the symbiotic origin of this domain from
eubacterial and archaebacterial lineages. However, the identity of
all the symbiotic lineages, and the number of symbiotic events are
still unclear. On one hand analyses purely based on similarity of
eukaryotic genes versus various prokaryotic lineages have failed to
detect a signal significantly stronger than others suggesting that
this method may be inadequate to investigate this question. On the
other hand phylogenetic analysis show various eukaryote/prokaryote
clusters – aside from the expected ones, eukaryote/α-proteobacteria
and eukaryote/cyanobacteria – albeit often supported by low
bootstrap values. Results from ongoing research will be presented
and compared with previous studies.
References:
Esser C, Ahmadinejad N,
Wiegand C, Rotte C, Sebastiani F, Gelius-Dietrich G, Henze K,
Krestmann E, Richly E, Leister D, Bryant D, Steel MA, Lockhart PJ,
Penny D, Martin W. (2004) A genome phylogeny for mitochondria among
α-proteobacteria and a predominantly eubacterial ancestry of yeast
nuclear genes. Molecular Biology and Evolution, 21:
1643-1660
|
|
| 12/14/05 |
Speaker: Dimitra Chalkia - Department of
Biology
Title: Gestalt Domain Detection Algorithm: a tool for detecting
highly diverged functional protein domains
Abstract: The plethora of protein sequences, that has been accumulated
the last decade, has led to an explosion in the appearance of
sequence-based computational methods for protein domain boundary
definition. Although these methods by definition do not provide
empirical data, they have proven to be one of the most convenient
and important tools for understanding the evolution of proteins and
their function. A new computational method designated the
Gestalt Domain Detection Algorithm
(GDDA), which can predict highly divergent functional domains, was
recently developed. The innovation of GDDA is that it modifies the
query protein sequence by inserting a segment of a consensus domain
sequence (seed) at every amino acid position of the query sequence.
The modification of the query sequence increases the sensitivity of
rps-BLAST, since the seed sequence provides a “constant” alignment
initiation sequence allowing BLAST to extend (i.e. ‘filling in the
gaps’ hence gestalt) the alignment even between highly divergent
sequences.
I will be presenting results on the
predictive ability of the GDDA by using positive controls and on the
experimental validation of GDDA predictions in the TEC protein
kinases and the TRP Channels.
References:
Altschul,S.F., Madden,T.L., Schaffer,A.A., Zhang,J.,
Zhang,Z., Miller,W., and Lipman,D.J. (1997). Gapped BLAST and
PSI-BLAST: a new generation of protein database search programs.
Nucleic Acids Res. 25, 3389-3402. Marchler-Bauer,A.,
Panchenko,A.R., Shoemaker,B.A., Thiessen,P.A., Geer,L.Y., and
Bryant,S.H. (2002). CDD: a database of conserved domain alignments
with links to domain three-dimensional structure. Nucleic Acids Res.
30, 281-283. Patterson,R.L., van Rossum,D.B., Nikolaidis,N.,
Gill,D.L., and Snyder,S.H. (2005). Phospholipase C-gamma: diverse
roles in receptor-mediated calcium signaling. Trends Biochem. Sci.
Ponting,C.P. and Russell,R.R. (2002). The natural history of protein
domains. Annu. Rev. Biophys. Biomol. Struct. 31, 45-71.
Ramsey,S.I., Delling,M., and Clapman,D.E. (2006). An introduction to
TPR Channels. Annu. Rev. Physiol. 68, 18.1-18.29 Smith,C.I.,
Islam,T.C., Mattsson,P.T., Mohamed,A.J., Nore,B.F., and Vihinen,M.
(2001). The Tec family of cytoplasmic tyrosine kinases: mammalian
Btk, Bmx, Itk, Tec, Txk and homologs in other species. Bioessays
23, 436-446. van Rossum,D.B., Patterson,R.L., Sharma,S.,
Barrow,R.K., Kornberg,M., Gill,D.L., and Snyder,S.H. (2005).
Phospholipase Cgamma1 controls surface expression of TRPC3 through
an intermolecular PH domain. Nature 434,
99-104. |
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