Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses. Proc Natl Acad Sci U S A 2012 Feb 21;109(8):E515-23
Date
02/07/2012Pubmed ID
22308498Pubmed Central ID
PMC3286982DOI
10.1073/pnas.1121626109Scopus ID
2-s2.0-84863118882 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two "neuronal" dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis.
Author List
Lou X, Fan F, Messa M, Raimondi A, Wu Y, Looger LL, Ferguson SM, De Camilli PAuthor
Xuelin Lou PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2
Cerebral Cortex
Dynamins
Mice
Mice, Knockout
Mutation
Neurons
Synaptic Transmission
Synaptic Vesicles
Up-Regulation
