Functional analysis of the domains of the C elegans Ror receptor tyrosine kinase CAM-1.
cam-1 encodes a Caenorhabditis elegans orphan receptor tyrosine kinase (RTK) of the Ror family that is required for cell migration and to orient cell polarity. Ror RTKs share a common domain structure. The predicted extracellular region contains immunoglobulin (Ig), cysteine-rich (CRD), and kringle (Kri) domains. Intracellularly are tyrosine kinase (Kin) and serine- and threonine (S/T)-rich domains. To investigate the functional requirement for CAM-1 domains in mediating cell migration, we engineered deletions that remove various domains and assessed the ability of these CAM-1 derivatives to rescue cam-1 mutant phenotypes. We find that the Ig, Kri, Kin, and S/T domains are dispensable for cell migration, but the CRD is required. Surprisingly, the entire intracellular region of CAM-1 is not required for proper cell migration. Most notably, a version of CAM-1 from which all domains besides the CRD and transmembrane domains have been deleted is able to rescue the migration of a single cell type, although not those of other cell types. Our results show that CAM-1 does not function exclusively as a canonical RTK and that it may function, at least in part, to regulate the distribution of a secreted ligand-possibly a Wnt protein.
Kim
Changsung
C
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Forrester
Wayne C
WC
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002465:Cell Movement; D016764:Cell Polarity; D003545:Cysteine; D004625:Embryo, Nonmammalian / Q000166:cytology; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000502:physiology*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors
D029742:Caenorhabditis elegans Proteins; C526267:CAM-1 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D003545:Cysteine