title: Akt/PKB controls the activity-dependent bulk endocytosis of synaptic vesicles.
abstract: 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.
authors.affiliation: Membrane Biology Group, Centre for Integrative Physiology, George Square, University of Edinburgh, Edinburgh EH8 9XD, UK.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Smillie
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cousin
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology; D034284:Dynamin I / Q000378:metabolism; D004558:Electric Stimulation; D004705:Endocytosis; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology*; D010766:Phosphorylation; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D034284:Dynamin I