Meeting report
[Congress Report]

Endocytosis and exocytosis

[Session speakers]Speakers from the Endocytosis and Exocytosis session. Left to right: Tom Kirchhausen, Phil Evans, Bryan Sutton, William Weis,Martin Lawrence, Axel T. Brunger, Peter Hwang, Ernst ter Haar.
Dramatic progress has been made to elucidate the structures of key components of membrane vesicular traffic, including those responsible for calcium-triggered neurotransmitter release, protein secretion, and hormone release. R.B. Sutton presented the structures of the synaptic fusion complex (a SNARE complex prototype) and the calcium sensor synaptotagmin. The free energy released by the assembly of the SNAREs probably leads to eventual fusion of the vesicle and target membrane. W.I. Weis presented the structures of the D2 and N-terminal domains of N-ethylmalemide-sensitive factor (NSF) (these two domains were solved independently in the Weis and A. Brunger laboratories) and proposed a mechanism for its function. NSF is an ATP-driven chaperone that dissociates the SNARE complex so that its components can engage in another fusion cycle. Equally dramatic progress has been made to elucidate the structures of proteins involved in vesicle formation and cargo selection during clathrin-mediated endocytosis. Clathrin is recruited to the plasma membrane, where it forms the coat that drives vesiculation and recruitment of the adaptor molecules that capture transmembrane receptors. E. Ter Haar presented the peptide-in-groove model to describe the structure of complexes between the N-terminal domain of clathrin and the clathrin-box binding motifs responsible for the recruitment of the adaptors to the clathrin coat. P. Hwang discussed the structure of a leg-segment of clathrin. P. Evans presented structures of several domains of the endocytic adaptor AP-2 complex. The m2 domain structure was solved in complex with peptides corresponding to the tyrosine-based sorting signals of a number of proteins and a general model for recognition was presented. The transferrin receptor is recruited by AP-2 adaptors and undergoes multiple rounds of clathrin-mediated endocytosis to import iron-loaded transferrin and is also a key component in human hereditary hemochromatosis, a prevalent genetic disease. M. Lawrence presented the structure of the complete ectodomain of human transferrin receptor and proposed a model to explain the recognition of transferrin by its receptor.

Axel T. Brunger and Thomas Kirchhausen