PMID- 38086519
OWN - NLM
STAT- MEDLINE
DCOM- 20240311
LR  - 20240311
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 128
DP  - 2024 Mar
TI  - The exocyst subunit Sec15 is critical for proper synaptic development and 
      function at the Drosophila NMJ.
PG  - 103914
LID - S1044-7431(23)00108-2 [pii]
LID - 10.1016/j.mcn.2023.103914 [doi]
AB  - The exocyst protein complex is important for targeted vesicle fusion in a variety 
      of cell types, however, its function in neurons is still not entirely known. We 
      found that presynaptic knockdown (KD) of the exocyst component sec15 by 
      transgenic RNAi expression caused a number of unexpected morphological and 
      physiological defects in the synapse. These include the development of active 
      zones (AZ) devoid of essential presynaptic proteins, an increase in the branching 
      of the presynaptic arbor, the appearance of satellite boutons, and a decrease in 
      the amplitude of stimulated postsynaptic currents as well as a decrease in the 
      frequency of spontaneous synaptic vesicle release. We also found the release of 
      extracellular vesicles from the presynaptic neuron was greatly diminished in the 
      Sec15 KDs. These effects were mimicked by presynaptic knockdown of Rab11, a 
      protein known to interact with the exocyst. sec15 RNAi expression caused an 
      increase in phosphorylated Mothers against decapentaplegic (pMad) in the 
      presynaptic terminal, an indication of enhanced bone morphogenic protein (BMP) 
      signaling. Some morphological phenotypes caused by Sec15 knockdown were reduced 
      by attenuation of BMP signaling through knockdown of wishful thinking (Wit), 
      while other phenotypes were unaffected. Individual knockdown of multiple proteins 
      of the exocyst complex also displayed a morphological phenotype similar to Sec15 
      KD. We conclude that Sec15, functioning as part of the exocyst complex, is 
      critically important for proper formation and function of neuronal synapses. We 
      propose a model in which Sec15 is involved in the trafficking of vesicles from 
      the recycling endosome to the cell membrane as well as possibly trafficking 
      extracellular vesicles for presynaptic release and these processes are necessary 
      for the correct structure and function of the synapse.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kang, Chris J
AU  - Kang CJ
AD  - Neuroscience Program, Amherst College, Amherst, MA 01002, United States of 
      America.
FAU - Guzman-Clavel, Luis E
AU  - Guzman-Clavel LE
AD  - Neuroscience Program, Amherst College, Amherst, MA 01002, United States of 
      America.
FAU - Lei, Katherine
AU  - Lei K
AD  - Neuroscience Program, Amherst College, Amherst, MA 01002, United States of 
      America.
FAU - Koo, Martin
AU  - Koo M
AD  - Neuroscience Program, Amherst College, Amherst, MA 01002, United States of 
      America.
FAU - To, Steven
AU  - To S
AD  - Neuroscience Program, Amherst College, Amherst, MA 01002, United States of 
      America.
FAU - Roche, John P
AU  - Roche JP
AD  - Neuroscience Program, Amherst College, Amherst, MA 01002, United States of 
      America; Department of Biology, Amherst College, Amherst, MA 01002, United States 
      of America. Electronic address: jroche@amherst.edu.
LA  - eng
PT  - Journal Article
DEP - 20231211
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Drosophila Proteins)
RN  - 0 (Sec15 protein, Drosophila)
RN  - 0 (Vesicular Transport Proteins)
SB  - IM
MH  - Animals
MH  - *Drosophila/metabolism
MH  - *Drosophila Proteins/metabolism
MH  - Animals, Genetically Modified/metabolism
MH  - Synapses/metabolism
MH  - Neurons/metabolism
MH  - Vesicular Transport Proteins/metabolism
OTO - NOTNLM
OT  - Exocyst
OT  - Extracellular vesicles
OT  - Rab11
OT  - Recycling endosome
OT  - Sec15
OT  - Synaptic transmission
COIS- Declaration of competing interest The authors declare no competing interest.
EDAT- 2023/12/13 00:42
MHDA- 2024/03/11 06:43
CRDT- 2023/12/12 19:18
PHST- 2023/08/25 00:00 [received]
PHST- 2023/12/04 00:00 [revised]
PHST- 2023/12/05 00:00 [accepted]
PHST- 2024/03/11 06:43 [medline]
PHST- 2023/12/13 00:42 [pubmed]
PHST- 2023/12/12 19:18 [entrez]
AID - S1044-7431(23)00108-2 [pii]
AID - 10.1016/j.mcn.2023.103914 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2024 Mar;128:103914. doi: 10.1016/j.mcn.2023.103914. Epub 2023 
      Dec 11.