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.
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