GTP hydrolysis triggers membrane remodeling by AMPH-1

Abstract

Membrane-enclosed transport carriers return biological molecules from the recycling endosome to the plasma membrane using a mechanism that is not well understood. In C. elegans, the formation of carriers from the recycling endosome requires the amphiphysin protein, AMPH-1. Recently, we found that purified AMPH-1 is sufficient for tubulation and vesiculation of liposomes in a mechanism that is regulated by guanine nucleotides. Here we propose a model linking GTP binding and hydrolysis to the membrane binding and tubulation required for transport carrier formation. We find that GTP binding stabilizes interactions between AMPH-1 and the membrane through amphipathic, N-terminal alpha helices, which are found at the tips of the arc-shaped, homodimeric structure. By contrast, in the post-hydrolysis, GDP-bound state, these helices are repositioned to interact with the N-terminal helices of other homodimers, to form an oligomeric AMPH-1 lattice that tubulates the membrane, in preparation for carrier formation by membrane fission.