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Published 11 October 2004. doi:10.1083/jcb.200406020
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 1, 43-50
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A role for talin in presynaptic function



Jennifer R. Morgan1,2, Gilbert Di Paolo1,2, Hauke Werner1,2, Valentina A. Shchedrina1,2, Marc Pypaert1, Vincent A. Pieribone3,4, and Pietro De Camilli1,2

1 Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519
2 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06519
3 Department of Physiology, Yale University School of Medicine, New Haven, CT 06519
4 John B. Pierce Laboratory, Yale University School of Medicine, New Haven, CT 06519

Correspondence to Pietro De Camilli: pietro.decamilli{at}yale.edu


Abstract

Talin, an adaptor between integrin and the actin cytoskeleton at sites of cell adhesion, was recently found to be present at neuronal synapses, where its function remains unknown. Talin interacts with phosphatidylinositol-(4)-phosphate 5-kinase type I{gamma}, the major phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]–synthesizing enzyme in brain. To gain insight into the synaptic role of talin, we microinjected into the large lamprey axons reagents that compete the talin–PIP kinase interaction and then examined their effects on synaptic structure. A dramatic decrease of synaptic actin and an impairment of clathrin-mediated synaptic vesicle endocytosis were observed. The endocytic defect included an accumulation of clathrin-coated pits with wide necks, as previously observed after perturbing actin at these synapses. Thus, the interaction of PIP kinase with talin in presynaptic compartments provides a mechanism to coordinate PI(4,5)P2 synthesis, actin dynamics, and endocytosis, and further supports a functional link between actin and clathrin-mediated endocytosis.

Abbreviations used in this paper: FERM, band 4.1/ezrin/radixin/moesin-like; ITC, isothermal titration calorimetry; PI(4,5)P2, phosphatidylinositol-(4,5)-bisphosphate; PIPKI{gamma}, phosphatidylinositol-(4)-phosphate 5-kinase type I{gamma}.


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