Date of Award


Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

De Camilli, Pietro V.


Effective neurotransmission is dependent on fast, reproduceable synaptic vesicle recycling. The synaptic vesicle recycling process is a complex event involving both protein-protein, as well as protein-lipid interactions. A central part of the retrieval process of synaptic vesicles lies in the ability of soluble proteins to deform the plasma membrane into a nascent bud which will eventually reform a fully competent synaptic vesicle upon fission. This process involves clathrin-coat proteins, which form a protein scaffold around the vesicle bud, as well as proteins which have more recently been thought to be involved in generating the high curvature membranes present at the tubular neck of the nascent vesicle bud.Endophilin 1, a protein highly enriched in the pre-synaptic neuronal subcompartment has been implicated in many stages of synaptic vesicle retrieval. The following work represents evidence of a direct role for endophilin in tubular membrane deformation, which may play an important part in the regeneration of synaptic vesicles. This behavior of endophilin complements that of one of its major pre-synaptic binding partners, dynamin, a large GTPase strongly implicated in the fission process of endocytosis. Endophilin forms a coordinated complex with dynamin along membrane tubules, and stabilizes these membrane tubules against the biomechanical changes imparted by dynamin to the membrane in a GTP-dependent manner.The membrane deforming motif in endophilin comprises a putative amphipathic helical region. This motif is conserved in amphiphysin, another major pre-synaptic dynamin binding partner implicated in synaptic vesicle recycling, and in another endophilin-related protein localized to the Golgi complex. Membrane deforming amphipathic helices have since been found in other proteins localized to additional cellular subcompartments, implicating this type of membrane interaction in diverse functions within the cell.

Open Access

This Article is Open Access