Adhesion

An elongating C. elegans embryo stained for HMP-1/α-catenin (green) and AJM-1 (red) [Jeff SImske].

Morphogenesis requires that cells make strong connections with one another. We are studying how the cadherin complex, which is conserved in all metazoans, regulates morphogenesis. We are using a variety of approaches to study the cadherin complex, including:

(1) Structure-function in the embryo to identify important regions in cadherin complex proteins;

hmp-2 wild-type vs. phosphomutant — Point mutations in a conserved tyrosine in HMP-2/β-catenin to probe the importance of key regulatory residues. *hmp-2(Y599F)::gfp* (phospho null; left) and *hmp-2(Y599E)::gfp* (phosphomimetic; right) [Tim Loveless].

Our structure-function work has been based on actual structures of C. elegans proteins; much of our earlier work was done in collaboration with Hee-Jung Choi (Seoul National University) and BIll Weis’s laboratory (Stanford University).

hmp-1 M domain — Space-filling overlay with ribbon structures of *C. elegans* HMP-1/a-catenin [collaboration with Hee-Jung Choi and Bill Weis].

(2) Single-molecule force spectroscopy to study the mechanical properties of cadherin complex proteins in collaboration with Yan Jie’s group (National University of Singapore/Mechanobioloogy Institute) to identify functionally important domains required for mechanotransduction. For an early preview of this work see this bioXriv preprint: Link.

(3) Functional genomics and proteomics to identify proteins and pathways that act in concert with the cadherin complex during morphogenesis. These include actin-binding and junctional proteins and the Slit/Robo GAP, SRGP-1.

SRGP-1 overexpression — Embryo expressing SRGP-1::GFP (green) stained for actin (purple). The inset shows extensive induced tubulations. [Ronen Zaidel-Bar].