GSK3-dependent control of SV recycling in mature nerve terminals. When GSK3 is active, it phosphorylates Ser774 on dynamin I, which inhibits the interaction between dynamin I and syndapin I. This interaction is essential for the triggering of activity-dependent bulk endocytosis (ADBE) and thus during high-intensity stimulation GSK3 is inhibited in an activity-dependent manner by Akt (action potential symbol). After stimulation, GSK3 is active and can rephosphorylate dynamin I. If the rephosphorylation of dynamin I by GSK3 is inhibited, the subsequent cycle of ADBE is arrested. Signal transduction cascades that may regulate GSK3 activity in the longer term are: a mammalian target of rapamycin (mTOR)/S6 kinase pathway (activated by amino acids), a PI3K/Akt pathway (activated by either insulin or growth factors), or a mitogen-activated protein kinase (MAPK)/MAPKAP-K1 pathway (activated by growth factors). GSK3 has no role in clathrin-mediated endocytosis (CME). GSK3 may perform an additional role in SV recycling by negatively regulating neurotransmitter release (dotted line). This is because GSK3 is proposed to phosphorylate P/Q-type calcium channels and inhibit calcium influx into the nerve terminal.
