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.
Highlights
We show that in primary cultures of cerebellar granule neurons the protein kinase Akt phosphorylates glycogen synthase kinase 3 (GSK3) during intense neuronal activity, ensuring that GSK3 is inactive during intense stimulation to aid dynamin I dephosphorylation
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
We have shown that Akt regulates Activity-dependent bulk endocytosis (ADBE) via its inhibition of presynaptic GSK3
Summary
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. During mild synaptic activity the dominant endocytosis mode is clathrin-mediated endocytosis (CME), which retrieves single SVs from the nerve terminal membrane [1,2]. The activities of both cdk and GSK3 are essential for maintaining subsequent rounds of ADBE [8,9] indicating dynamin I rephosphorylation is important as its dephosphorylation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
