PMID- 35426896
OWN - NLM
STAT- MEDLINE
DCOM- 20220419
LR  - 20240214
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 221
IP  - 5
DP  - 2022 May 2
TI  - SNX5 targets a monoamine transporter to the TGN for assembly into dense core 
      vesicles by AP-3.
LID - 10.1083/jcb.202106083 [doi]
LID - e202106083
AB  - The time course of signaling by peptide hormones, neural peptides, and other 
      neuromodulators depends on their storage inside dense core vesicles (DCVs). 
      Adaptor protein 3 (AP-3) assembles the membrane proteins that confer regulated 
      release of DCVs and is thought to promote their trafficking from endosomes 
      directly to maturing DCVs. We now find that regulated monoamine release from DCVs 
      requires sorting nexin 5 (SNX5). Loss of SNX5 disrupts trafficking of the 
      vesicular monoamine transporter (VMAT) to DCVs. The mechanism involves a role for 
      SNX5 in retrograde transport of VMAT from endosomes to the TGN. However, this 
      role for SNX5 conflicts with the proposed function of AP-3 in trafficking from 
      endosomes directly to DCVs. We now identify a transient role for AP-3 at the TGN, 
      where it associates with DCV cargo. Thus, retrograde transport from endosomes by 
      SNX5 enables DCV assembly at the TGN by AP-3, resolving the apparent antagonism. 
      A novel role for AP-3 at the TGN has implications for other organelles that also 
      depend on this adaptor.
CI  - (c) 2022 Xu et al.
FAU - Xu, Hongfei
AU  - Xu H
AUID- ORCID: 0000-0003-1381-2123
AD  - Departments of Neurology and Physiology, University of California San Francisco, 
      San Francisco, CA.
AD  - Jiangsu Key Laboratory of Xenotransplantation, School of Basic Medical Science, 
      Nanjing Medical University, Nanjing, China.
FAU - Chang, Fei
AU  - Chang F
AD  - Jiangsu Key Laboratory of Xenotransplantation, School of Basic Medical Science, 
      Nanjing Medical University, Nanjing, China.
FAU - Jain, Shweta
AU  - Jain S
AD  - Departments of Neurology and Physiology, University of California San Francisco, 
      San Francisco, CA.
FAU - Heller, Bradley Austin
AU  - Heller BA
AD  - Departments of Neurology and Physiology, University of California San Francisco, 
      San Francisco, CA.
FAU - Han, Xu
AU  - Han X
AD  - Jiangsu Key Laboratory of Xenotransplantation, School of Basic Medical Science, 
      Nanjing Medical University, Nanjing, China.
FAU - Liu, Yongjian
AU  - Liu Y
AD  - Jiangsu Key Laboratory of Xenotransplantation, School of Basic Medical Science, 
      Nanjing Medical University, Nanjing, China.
AD  - Departments of Pharmacology and Biological Chemistry, University of Pittsburgh, 
      Pittsburgh, PA.
FAU - Edwards, Robert H
AU  - Edwards RH
AUID- ORCID: 0000-0002-8650-3260
AD  - Departments of Neurology and Physiology, University of California San Francisco, 
      San Francisco, CA.
LA  - eng
GR  - R01 MH050712/MH/NIMH NIH HHS/United States
GR  - R01 NS103938/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220415
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Adaptor Protein Complex 3)
RN  - 0 (Carrier Proteins)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Sorting Nexins)
SB  - IM
MH  - *Adaptor Protein Complex 3/metabolism
MH  - Biological Transport
MH  - Carrier Proteins/metabolism
MH  - *Dense Core Vesicles/metabolism
MH  - *Endosomes/metabolism
MH  - Neurotransmitter Agents/metabolism
MH  - Protein Transport
MH  - *Sorting Nexins/metabolism
PMC - PMC9016777
EDAT- 2022/04/16 06:00
MHDA- 2022/04/20 06:00
PMCR- 2022/11/02
CRDT- 2022/04/15 12:08
PHST- 2021/06/15 00:00 [received]
PHST- 2021/12/06 00:00 [revised]
PHST- 2022/02/16 00:00 [accepted]
PHST- 2022/04/15 12:08 [entrez]
PHST- 2022/04/16 06:00 [pubmed]
PHST- 2022/04/20 06:00 [medline]
PHST- 2022/11/02 00:00 [pmc-release]
AID - 213147 [pii]
AID - jcb.202106083 [pii]
AID - 10.1083/jcb.202106083 [doi]
PST - ppublish
SO  - J Cell Biol. 2022 May 2;221(5):e202106083. doi: 10.1083/jcb.202106083. Epub 2022 
      Apr 15.