Defining the mechanism of PlexinA3 activation by Sema3d

Signaling pathways are critical for communication between cells during the growth and development of multicellular organisms. For example, signaling through the secreted semaphorin signaling molecules has been shown to mediate diverse cellular functions, including cell adhesion, cell migration, tissue patterning, cell proliferation, viability, and changes in the cytoskeleton. Semaphorins utilize different types of membrane receptors, including the Plexins (Plxns) and the Neuropilins (Nrps). However, it remains unclear how Sema signaling influences its receptors to affect downstream cellular outcomes.  Signaling via Sema3d was found to influence both cell division and joint formation during regeneration of the zebrafish fin skeleton. Recent findings suggest that Sema3d-Nrp2a signaling influences cell division and that Sema3d-PlxnA3 signaling influences joint formation.

 

The goals of this proposal are to utilize purified Sema3d in functional assays both in vivo and in vitro, and to utilize purified domains of PlxnA3 to define the requirements for receptor activation. Completion of these Aims will provide novel insights into the mechanisms underlying the activities of the Sema3d-PlxnA3 signaling system.