Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter

被引：42

作者：

Chua, John Jia En ^{[2
]}

Butkevich, Eugenia ^{[1
]}

Worseck, Josephine M. ^{[4
]}

Kittelmann, Maike ^{[5
,6
]}

Gronborg, Mads ^{[2
]}

Behrmann, Elmar ^{[2
]}

Stelzl, Ulrich ^{[4
]}

Pavlos, Nathan J. ^{[2
]}

Lalowski, Maciej M. ^{[7
]}

Eimer, Stefan ^{[5
,6
]}

Wanker, Erich E. ^{[7
]}

Klopfenstein, Dieter Robert ^{[1
,3
]}

Jahn, Reinhard ^{[2
]}

机构：

[1] Univ Gottingen, Drittes Phys Inst Biophys, D-37077 Gottingen, Germany

[2] Max Planck Inst Biophys Chem, Dept Neurobiol, D-37077 Gottingen, Germany

[3] Univ Gottingen, D-37073 Gottingen, Germany

[4] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

[5] European Neurosci Inst Gottingen, D-37077 Gottingen, Germany

[6] German Res Fdn Res Ctr Mol Physiol Brain, D-37077 Gottingen, Germany

[7] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 15期

关键词：

fasciculation and elongation protein zeta 1; transport defect; cargo aggregation; PROTEIN-INTERACTION NETWORK; CAENORHABDITIS-ELEGANS; PC12; CELLS; MOTOR; VESICLE; COMPLEX; GENE; MUNC18-1; SNAP-25; FEZ1;

D O I：

10.1073/pnas.1113819109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Presynaptic nerve terminals are formed from preassembled vesicles that are delivered to the prospective synapse by kinesin-mediated axonal transport. However, precisely how the various cargoes are linked to the motor proteins remains unclear. Here, we report a transport complex linking syntaxin 1a (Stx) and Munc18, two proteins functioning in synaptic vesicle exocytosis at the presynaptic plasma membrane, to the motor protein Kinesin-1 via the kinesin adaptor FEZ1. Mutation of the FEZ1 ortholog UNC-76 in Caenorhabditis elegans causes defects in the axonal transport of Stx. We also show that binding of FEZ1 to Kinesin-1 and Munc18 is regulated by phosphorylation, with a conserved site (serine 58) being essential for binding. When expressed in C. elegans, wild-type but not phosphorylation-deficient FEZ1 (S58A) restored axonal transport of Stx. We conclude that FEZ1 operates as a kinesin adaptor for the transport of Stx, with cargo loading and unloading being regulated by protein kinases.

引用

页码：5862 / 5867

页数：6

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