How to Build a Clathrin-Coated Vesicle: Switches, Timers & Scaffolding

  • 1 April 2021
    4:00 PM

Speaker

Zuzana Kadlecová, Ph. D.

Principal investigator at Cambridge Institute for Medical Research, UK; Recent holder of GACR Junior Star Grant

"We are a cell biology laboratory interested in gaining a better understanding of the molecular regulation of endocytosis and its integration within wider cell signaling and metabolic homeostasis.

Recently, our collaborative efforts identified the molecular basis of the NAK kinase-mediated phosphorylation of the most abundant clathrin adaptor, AP2 (link to paper). We showed that AP2 phosphorylation not only leads to changes in its interactome, but is a major decision point in clathrin-mediated endocytosis, capable of affecting its rates.

We are building on these findings by exploring systematically and mechanistically how kinases and phosphatases regulate clathrin-mediated endocytosis. We focus on NAK kinases, which are also recent drug development targets for neuropathic pain, and were linked by GWAS to an increased neurodegeneration risk."

See more information at Dr. Kadlecová´s research group website.

About the lecture

At least 90% of the plasma membrane turnover in epithelial cells is controlled by clathrin-mediated endocytosis (CME). The selectivity and rates of CME impacts diverse cell biological processes including cellular metabolism and synaptic vesicle reformation. And yet, it is inherently difficult to study CME due to the heterogeneity, high frequency and short time scale at which the formation of clathrin-coated vesicles occur.

In my lab we apply an integrative approach to study regulation of CME. To this end we have developed quantitative computational approaches in combination with the sensitive high resolution and super-resolution live cell microscopy.

In my talk I will discuss several fundamental molecular pathways governing the kinetic rates of CME that we have identified and dissected with the excellent temporal resolution and robust signal-to-noise ratio of these tools.

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