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Regulation of neuromuscular junction organization by Rab2 and its effector ICA69 in Drosophila

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Title Regulation of neuromuscular junction organization by Rab2 and its effector ICA69 in Drosophila
 
Creator Mallik, Bhagaban
Dwivedi, Manish Kumar
Mushtaq, Zeeshan
Kumari, Manisha
Verma, Praveen K.
Kumar, Vimlesh
 
Subject Neuromuscular junction
dICA69
BAR domain
α-Spectrin
dRab2
Glutamate receptors
 
Description Accepted date: April 19, 2017
Mechanisms underlying synaptic differentiation, which involves neuronal membrane and cytoskeletal remodeling, are not completely understood. We performed a targeted RNAi-mediated screen of Drosophila BAR-domain proteins and identified islet cell autoantigen 69 kDa (dICA69) as one of the key regulators of morphological differentiation of larval neuromuscular junction (NMJ). We show that Drosophila ICA69 colocalizes with α-Spectrin at the NMJ. The conserved N-BAR domain of dICA69 deforms liposomes in vitro Full length and ICAC but not the N-BAR domain of dICA69 induces filopodia in cultured cells. Consistent with its cytoskeleton regulatory role, dICA69 mutant show reduced α-Spectrin immunoreactivity at the larval NMJ. Manipulating levels of dICA69 or its interactor dPICK1 alters synaptic level of ionotropic glutamate receptors (iGluRs). Moreover, reducing dPICK1 or dRab2 levels phenocopies dICA69 mutation. Interestingly, dRab2 regulates not only synaptic iGluR but also dICA69 levels. Thus, our data suggest that: a) dICA69 regulates NMJ organization through a pathway that involves dPICK1 and dRab2, and b) dRab2 genetically functions upstream of dICA69 and regulates NMJ organization and targeting/retention of iGluRs by regulating dICA69 levels.
This work was supported by a project grant from the Department of Biotechnology (BT/PR-
15163/GBD/27/349/2011) and SERB (SR/FT/LS-103/2010); Government of India to VK and
intramural funds from IISER Bhopal.
 
Date 2017-05-04T08:54:21Z
2017-05-04T08:54:21Z
2017
 
Type Article
 
Identifier Development, 144(11): 2032-2044
1477-9129
http://59.163.192.83:8080/jspui/handle/123456789/744
http://dev.biologists.org/content/early/2017/04/27/dev.145920.long
10.1242/dev.145920
 
Language en_US
 
Publisher The Company of Biologists