Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan

被引：68

作者：

Ch'ng, QueeLim ^{[1
]}

Sieburth, Derek ^{[1
]}

Kaplan, Joshua M. ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

来源：

PLOS GENETICS | 2008年 / 4卷 / 11期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

D O I：

10.1371/journal.pgen.1000283

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Cells are organized into distinct compartments to perform specific tasks with spatial precision. In neurons, presynaptic specializations are biochemically complex subcellular structures dedicated to neurotransmitter secretion. Activity-dependent changes in the abundance of presynaptic proteins are thought to endow synapses with different functional states; however, relatively little is known about the rules that govern changes in the composition of presynaptic terminals. We describe a genetic strategy to systematically analyze protein localization at Caenorhabditis elegans presynaptic specializations. Nine presynaptic proteins were GFP-tagged, allowing visualization of multiple presynaptic structures. Changes in the distribution and abundance of these proteins were quantified in 25 mutants that alter different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components and provides a new method to compare gene functions by identifying shared protein localization phenotypes. Using this strategy, we identified several genes that regulate secretion of insulin-like growth factors (IGFs) and influence lifespan in a manner dependent on insulin/IGF signaling.

引用

页数：15

共 84 条

[1] The two isoforms of the Caenorhabditis elegans leukocyte-common antigen related receptor tyrosine phosphatase PTP-3 function independently in axon guidance and synapse formation [J].

Ackley, BD ;

Harrington, RJ ;

Hudson, ML ;

Williams, L ;

Kenyon, CJ ;

Chisholm, AD ;

Jin, Y .

JOURNAL OF NEUROSCIENCE, 2005, 25 (33) :7517-7528

[2] Neurosecretory control of aging in Caenorhabditis elegans [J].

Ailion, M ;

Inoue, T ;

Weaver, CI ;

Holdcraft, RW ;

Thomas, JH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) :7394-7397

[3] Novel Ca2+-binding protein (CAPS) related to UNC-31 required for Ca2+-activated exocytosis [J].

Ann, K ;

Kowalchyk, JA ;

Loyet, KM ;

Martin, TFJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (32) :19637-19640

[4] Regulation of lifespan by sensory perception in Caenorhabditis elegans [J].

Apfeld, J ;

Kenyon, C .

NATURE, 1999, 402 (6763) :804-809

[5] Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic [J].

Balklava, Zita ;

Pant, Saumya ;

Fares, Hanna ;

Grant, Barth D. .

NATURE CELL BIOLOGY, 2007, 9 (09) :1066-U35

[6]

BENNETT DL, 1992, J BIOL CHEM, V267, P15229

[7] Colocalization of synapsin and actin during synaptic vesicle recycling [J].

Bloom, O ;

Evergren, E ;

Tomilin, N ;

Kjaerulff, O ;

Löw, P ;

Brodin, L ;

Pieribone, VA ;

Greengard, P ;

Shupliakov, O .

JOURNAL OF CELL BIOLOGY, 2003, 161 (04) :737-747

[8] Mutations in a C-elegans G(q)alpha gene disrupt movement, egg laying, and viability [J].

Brundage, L ;

Avery, L ;

Katz, A ;

Kim, UJ ;

Mendel, JE ;

Sternberg, PW ;

Simon, MI .

NEURON, 1996, 16 (05) :999-1009

[9] Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C-elegans [J].

Burbea, M ;

Dreier, L ;

Dittman, JS ;

Grunwald, ME ;

Kaplan, JM .

NEURON, 2002, 35 (01) :107-120

[10] The SAD-1 kinase regulates presynaptic vesicle clustering and axon termination [J].

Crump, JG ;

Zhen, M ;

Jin, Y ;

Bargmann, CI .

NEURON, 2001, 29 (01) :115-129

← 1 2 3 4 5 6 7 8 9 →