Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Monday Speaker Abstracts

Maturation of Clathrin-coated Vesicles Requires Dynamic Instability and Processivity Harvey McMahon . MRC Laboratory of Molecular Biology, United Kingdom. Clathrin-mediated endocytosis (CME) is a dynamic process that is important for synaptic vesicle retrieval, receptor uptake and virus internalisation. More than thirty interacting proteins have been identified in this pathway, their interactions studied in vitro and the temporal recruitment patterns mapped in vivo . How does a complicated network of protein interactions give rise to the emergent property of clathrin-coated vesicle budding? We find the network is wired for processivity via overlapping short motifs in intrinsically disordered protein domains binding to competing adaptors (FCHo2 and AP2). This inherent competition gives rise to dynamic instability, constant co-existence of assembly and disassembly, and the arrangement of competition between modules determines directionality. I will discuss the two major functional consequences of disrupting the CME network. While the network is robust and withstands minor perturbations, there is a correlation between the strength of CME inhibition and the way the network has reacted. We will explore the implications of this analysis.

- 37 -