CHL1 Is a Selective Organizer of the Presynaptic Machinery Chaperoning the SNARE Complex

被引:48
作者
Andreyeva, Aksana [1 ,4 ]
Leshchyns'ka, Iryna [1 ,3 ]
Knepper, Michael [1 ]
Betzel, Christian [2 ]
Redecke, Lars [2 ]
Sytnyk, Vladimir [1 ,3 ]
Schachner, Melitta [1 ,5 ,6 ]
机构
[1] Univ Hamburg, Zentrum Mol Neurobiol, Hamburg, Germany
[2] Univ Hamburg, Inst Biochem & Mol Biol, Hamburg, Germany
[3] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia
[4] Univ Dusseldorf, Inst Neuro & Sensory Physiol, Dusseldorf, Germany
[5] Shantou Univ, Coll Med, Ctr Neurosci, Shantou, Peoples R China
[6] Rutgers State Univ, Keck Ctr Collaborat Neurosci, Piscataway, NJ USA
关键词
CYSTEINE-STRING PROTEIN; ADHESION MOLECULE L1; CLOSE HOMOLOG; MICE DEFICIENT; CALL GENE; ASSOCIATION; BINDING; CSP; PHOSPHORYLATION; OLIGOMERIZATION;
D O I
10.1371/journal.pone.0012018
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
Proteins constituting the presynaptic machinery of vesicle release undergo substantial conformational changes during the process of exocytosis. While changes in the conformation make proteins vulnerable to aggregation and degradation, little is known about synaptic chaperones which counteract these processes. We show that the cell adhesion molecule CHL1 directly interacts with and regulates the activity of the synaptic chaperones Hsc70, CSP and alpha SGT. CHL1, Hsc70, CSP and alpha SGT form predominantly CHL1/Hsc70/alpha SGT and CHL1/CSP complexes in synapses. Among the various complexes formed by CHL1, Hsc70, CSP and alpha SGT, SNAP25 and VAMP2 induce chaperone activity only in CHL1/Hsc70/alpha SGT and CHL1/CSP complexes, respectively, indicating a remarkable selectivity of a presynaptic chaperone activity for proteins of the exocytotic machinery. In mice with genetic ablation of CHL1, chaperone activity in synapses is reduced and the machinery for synaptic vesicle exocytosis and, in particular, the SNARE complex is unable to sustain prolonged synaptic activity. Thus, we reveal a novel role for a cell adhesion molecule in selective activation of the presynaptic chaperone machinery.
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页数:20
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共 56 条
[1]  
Angeloni D, 1999, AM J MED GENET, V86, P482, DOI 10.1002/(SICI)1096-8628(19991029)86:5<482::AID-AJMG15>3.0.CO
[2]  
2-L
[3]   Two single nucleotide polymorphisms (SNPs) in the CALL gene for association studies with IQ [J].
Angeloni, D ;
Wei, MH ;
Lerman, MI .
PSYCHIATRIC GENETICS, 1999, 9 (03) :165-167
[4]   ATP releases HSP-72 from protein aggregates after renal ischemia [J].
Aufricht, C ;
Lu, E ;
Thulin, G ;
Kashgarian, M ;
Siegel, NJ ;
Van Why, SK .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1998, 274 (02) :F268-F274
[5]   NCAM induces CaMKIIα-mediated RPTPα phosphorylation to enhance its catalytic activity and neurite outgrowth [J].
Bodrikov, Vsevolod ;
Sytnyk, Vladimir ;
Leshchyns'ka, Iryna ;
den Hertog, Jeroen ;
Schachner, Melitta .
JOURNAL OF CELL BIOLOGY, 2008, 182 (06) :1185-1200
[6]   Drosophila Hsc70-4 is critical for neurotransmitter exocytosis in vivo [J].
Bronk, P ;
Wenniger, JJ ;
Dawson-Scully, K ;
Guo, XF ;
Hong, S ;
Atwood, HL ;
Zinsmaier, KE .
NEURON, 2001, 30 (02) :475-488
[7]   The multiple functions of cysteine-string protein analyzed at Drosophila nerve terminals [J].
Bronk, P ;
Nie, ZP ;
Klose, MK ;
Dawson-Scully, K ;
Zhang, JH ;
Robertson, RM ;
Atwood, HL ;
Zinsmaier, KE .
JOURNAL OF NEUROSCIENCE, 2005, 25 (09) :2204-2214
[8]   Close homolog of L1 is an enhancer of integrin-mediated cell migration [J].
Buhusi, M ;
Midkiff, BR ;
Gates, AM ;
Richter, M ;
Schachner, M ;
Maness, PF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (27) :25024-25031
[9]   Cysteine string protein functions directly in regulated exocytosis [J].
Chamberlain, LH ;
Burgoyne, RD .
MOLECULAR BIOLOGY OF THE CELL, 1998, 9 (08) :2259-2267
[10]   The molecular chaperone function of the secretory vesicle cysteine string proteins [J].
Chamberlain, LH ;
Burgoyne, RD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (50) :31420-31426