Abstract: Series 100, Lecture 1

The Harvey Lectures Series 100 (2004—2005)

next lecture

Lecture #1: Thursday, October 21, 2004 — Time and Location

Molecular Mechanisms in Membrane Traffic at the Neuronal Synapse: Role of Protein-Lipid Interactions

Pietro De Camilli, MD

Eugene Higgins Professor of Cell Biology
Investigator, Howard Hughes Medical Institute
Department of Cell Biology

Howard Hughes Medical Institute, Yale University School of Medicine

New Haven, Connecticut

Neuronal synapses are cell-cell junctions where electrical signals are propagated across cell membranes via chemical intermediates called neurotransmitters. Both sides of the synapse rely for their functions on specialized forms of vesicular transport. Presynaptically, “synaptic” vesicles are responsible for the storage of neurotransmitters and for their secretion by regulated fusion (exocytosis) with the plasma membrane. Following exocytosis, their membranes are rapidly retrieved by endocytosis and recycled. Postsynaptically, exo-endocytic vesicle traffic regulates the number of neurotransmitter receptors in the plasma membrane. In the last several years much progress has been made in the characterization of the protein machinery responsible for the biogenesis, exocytosis and endocytic recycling of vesicles at the synapse. A less investigated area of research concerns the role of lipids of the membrane bilayer in the regulation of these processes. Interactions between cytosolic proteins and both the hydrophobic core and the hydrophilic head groups of membrane lipids have important roles in membrane deformation, membrane transport, membrane fusion and fission. In addition, phosphorylation-dephosphorylation of a class of membrane phospholipids, the inositol phospholipids, represents an important mechanism in the control of vectorial membrane transport within the synapse. The talk will focus on our cell biological and genetic studies in this area and will emphasize general principles in membrane traffic emerging from this research.