Meet the nodes, “clustered hubs” and links of clathrin-mediated endocytosis

vesicleformation2Network biology is a way to integrate fragmented benchwork data in order to understand complex biological phenomena. In a recent Nature paper, entitled Integrating molecular and network biology to decode endocytosis Cambridge (UK) researchers authors Eva Schmid and Harvey McMahon of MRC, Cambridge give a good example of a predictive and experimentally useful systems biology approach. As in many cases in the current literature, the formal, printed article is just the tip of the iceberg, and the “supplementary informationsection is as crucial.

Clathrin-mediated endocytosis (CME) is an important vesicle biogenesis pathway. Cargo is packaged into vesicles that are surrounded by a coat predominantly made of the protein clathrin and adaptor protein complexes. For instance at the synapse, clathrin-coated vesicles (CCVs) participate in retrieval of synaptic vesicles following exocytosis.

vesicleformation3Authors identify 2 hubs in this pathway: AP2 and clathrin triskelion and instead of putting them into the existing hub subtypes (‘date’ and ‘party’ hubs) they argue that neither are hubs at the beginning of CME, but mature into hubs by clustering either on the membrane or through polymerization. It is likely that many pathway/party hub proteins will oligomerize or cluster to function as pathway hubs. ‘Clustered hubs’ are a new subtype of hubs not previously described

I found Figure 3 particulary refreshing which depicts functional and connectivity views of vesicle formation in nerve terminals. (2 pieces included)

Experimentally testable consequences of the study:

good test for proteins that function as hubs only when clustered in space and time is that overexpression of such a protein should not have any phenotype on the pathway.

overexpression of nodes that bind directly to hubs would be predicted to have disastrous affects owing to titration of hub interaction points