How are synaptic How are synaptic vesicles clustered? vesicles clustered?

Daniel Gitler, Department of Daniel Gitler, Department of Physiology and Cell biology, Physiology and Cell biology,

Faculty of Health Sciences and Faculty of Health Sciences and Zlotowski Center for Zlotowski Center for

Neuroscience, Ben-Gurion Neuroscience, Ben-Gurion University of the NegevUniversity of the Negev

Presynaptic terminalPresynaptic terminal

Postsynaptic Postsynaptic terminalterminal

Gitler et al., J Neurosci 2004

Vesicles redistribute into the axon when synapsins are ablated

500 nm

Orenbuch et al., J Neurosci 2012

0 10 20 30 400.0

0.2

0.4

0.6

1.0 SypI-EGFP

TKO

Flu

ores

cenc

e R

ecov

ery

Time (min)

WT

Measuring vesicle mobilityW

T

Before Bleach Recovery

Darcy at al. 2006

Orenbuch et al., J Neurosci 2012

Model for vesicle clustering

Synapsins are ATP binding proteins

Esser et al., 1998

Crystalographic structure of ATP bound to the central domain of synapsin I

Do mutations in ATP binding sites affect clustering and mobilization of vesicles?

Other topics

• Does mobilization of reserve vesicles require endocytosis?

• The basis for epilepsy in the synapsin TKO mice and in cases of human familial epilepsy linked to synapsin

• The possibility of a functional interaction between synapsin and alpha-synuclein, a protein involved in Parkinsons disease