σ2-Adaptin Facilitates Basal Synaptic Transmission and Is Required for Regenerating Endo-Exo Cycling Pool Under High-Frequency Nerve Stimulation in Drosophila.

Autor:	Choudhury SD; Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, Govindpura-Bhopal 462 023, Madhya Pradesh, India., Mushtaq Z; Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, Govindpura-Bhopal 462 023, Madhya Pradesh, India., Reddy-Alla S; Institute for Biology/Genetics, Free University of Berlin, 14195 Berlin, Germany., Balakrishnan SS; National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560 065, India., Thakur RS; Shanmugha Arts, Science,Technology and Research Academy, Thanjavar 613401, India., Krishnan KS; National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560 065, India., Raghu P; National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560 065, India., Ramaswami M; National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560 065, India Trinity College Institute of Neuroscience (TCIN), Trinity College Dublin, University of Dublin, Dublin 2, Ireland., Kumar V; Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, Govindpura-Bhopal 462 023, Madhya Pradesh, India vimlesh@iiserb.ac.in.
Jazyk:	angličtina
Zdroj:	Genetics [Genetics] 2016 May; Vol. 203 (1), pp. 369-85. Date of Electronic Publication: 2016 Feb 26.
DOI:	10.1534/genetics.115.183863
Abstrakt:	The functional requirement of adapter protein 2 (AP2) complex in synaptic membrane retrieval by clathrin-mediated endocytosis is not fully understood. Here we isolated and functionally characterized a mutation that dramatically altered synaptic development. Based on the aberrant neuromuscular junction (NMJ) synapse, we named this mutation angur (a Hindi word meaning "grapes"). Loss-of-function alleles of angur show more than twofold overgrowth in bouton numbers and a dramatic decrease in bouton size. We mapped the angur mutation to σ2-adaptin, the smallest subunit of the AP2 complex. Reducing the neuronal level of any of the subunits of the AP2 complex or disrupting AP2 complex assembly in neurons phenocopied the σ2-adaptin mutation. Genetic perturbation of σ2-adaptin in neurons leads to a reversible temperature-sensitive paralysis at 38°. Electrophysiological analysis of the mutants revealed reduced evoked junction potentials and quantal content. Interestingly, high-frequency nerve stimulation caused prolonged synaptic fatigue at the NMJs. The synaptic levels of subunits of the AP2 complex and clathrin, but not other endocytic proteins, were reduced in the mutants. Moreover, bone morphogenetic protein (BMP)/transforming growth factor β (TGFβ) signaling was altered in these mutants and was restored by normalizing σ2-adaptin in neurons. Thus, our data suggest that (1) while σ2-adaptin facilitates synaptic vesicle (SV) recycling for basal synaptic transmission, its activity is also required for regenerating SVs during high-frequency nerve stimulation, and (2) σ2-adaptin regulates NMJ morphology by attenuating TGFβ signaling. (Copyright © 2016 by the Genetics Society of America.)
Databáze:	MEDLINE
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