PMID- 22487004
OWN - NLM
STAT- MEDLINE
DCOM- 20121004
LR  - 20211021
IS  - 1600-0854 (Electronic)
IS  - 1398-9219 (Print)
IS  - 1398-9219 (Linking)
VI  - 13
IP  - 7
DP  - 2012 Jul
TI  - Akt/PKB controls the activity-dependent bulk endocytosis of synaptic vesicles.
PG  - 1004-11
LID - 10.1111/j.1600-0854.2012.01365.x [doi]
AB  - Activity-dependent bulk endocytosis (ADBE) is the dominant SV endocytosis mode 
      during intense neuronal activity. The dephosphorylation of Ser774 on dynamin I is 
      essential for triggering of ADBE, as is its subsequent rephosphorylation by 
      glycogen synthase kinase 3 (GSK3). We show that in primary cultures of cerebellar 
      granule neurons the protein kinase Akt phosphorylates GSK3 during intense 
      neuronal activity, ensuring that GSK3 is inactive during intense stimulation to 
      aid dynamin I dephosphorylation. Furthermore, when a constitutively active form 
      of Akt was overexpressed in primary neuronal cultures, ADBE was inhibited with no 
      effect on clathrin-mediated endocytosis. Thus Akt has two major regulatory roles 
      (i) to ensure efficient dynamin I dephosphorylation via acute activity-dependent 
      inhibition of GSK3 and (ii) to negatively regulate ADBE when activated in the 
      longer term. This is the first demonstration of a role for Akt in SV recycling 
      and suggests a key role for this protein kinase in modulating synaptic strength 
      during elevated neuronal activity.
CI  - (c) 2012 John Wiley & Sons A/S.
FAU - Smillie, Karen J
AU  - Smillie KJ
AD  - Membrane Biology Group, Centre for Integrative Physiology, George Square, 
      University of Edinburgh, Edinburgh EH8 9XD, UK.
FAU - Cousin, Michael A
AU  - Cousin MA
LA  - eng
GR  - 084277/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120429
PL  - England
TA  - Traffic
JT  - Traffic (Copenhagen, Denmark)
JID - 100939340
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.5.1.50 (Dynamin I)
SB  - IM
MH  - Animals
MH  - Cerebellum/cytology
MH  - Dynamin I/metabolism
MH  - Electric Stimulation
MH  - *Endocytosis
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Neurons/*enzymology
MH  - Phosphorylation
MH  - Primary Cell Culture
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Synaptic Vesicles/*metabolism
PMC - PMC3488115
EDAT- 2012/04/11 06:00
MHDA- 2012/10/05 06:00
CRDT- 2012/04/11 06:00
PHST- 2012/01/12 00:00 [received]
PHST- 2012/04/04 00:00 [revised]
PHST- 2012/04/09 00:00 [accepted]
PHST- 2012/04/11 06:00 [entrez]
PHST- 2012/04/11 06:00 [pubmed]
PHST- 2012/10/05 06:00 [medline]
AID - 10.1111/j.1600-0854.2012.01365.x [doi]
PST - ppublish
SO  - Traffic. 2012 Jul;13(7):1004-11. doi: 10.1111/j.1600-0854.2012.01365.x. Epub 2012 
      Apr 29.