The Calponin Family Member CHDP-1 Interacts with Rac/CED-10 to Promote Cell Protrusions

Eukaryotic cells extend a variety of surface protrusions to direct cell motility. Formation of protrusions is mediated by coordinated actions between the plasma membrane and the underlying actin cytoskeleton. Here, we found that the single calponin homology (CH) domain-containing protein CHDP-1 induces the formation of cell protrusions in C. elegans. CHDP-1 is anchored to the cortex through its amphipathic helix. CHDP-1 associates through its CH domain with the small GTPase Rac1/CED-10, which is a key regulator of the actin cytoskeleton. CHDP-1 preferentially binds to the GTP-bound active form of the CED-10 protein and preserves the membrane localization of GTP-CED-10. Hence, by coupling membrane expansion to Rac1-mediated actin dynamics, CHDP-1 promotes the formation of cellular protrusions in vivo.
Author Summary In response to intra- and extracellular cues, remodeling of the sub-membranous cortical actin cytoskeleton constantly reorganizes the plasma membrane. Thus, distinct types of actin-rich invaginations or protrusions, such as filopodia and lamellipodia, enable cells to explore territory and pull themselves around. Extensive research has shown that the plasma membrane is tightly coupled to the motility machinery. However, how the continuous reorganization of the actin cytoskeleton is coupled with appropriate restructuring of the plasma membrane at the molecular level in vivo is unclear. Here, we identified that the single calponin homology (CH) domain-containing protein CHDP-1 promotes the formation of cell protrusions in C. elegans. CHDP-1 localizes to the cell cortex and through its calponin homology (CH) domain, CHDP-1 directly binds to the master actin regulator Rac1/CED-10 and enhances the membrane localization of the active CED-10 protein. Thus, we discovered a novel CHDP-1/Rac1 module which effectively couples membrane expansion to cortex actin dynamics in vivo.