title: C. elegans patched-3 is an essential gene implicated in osmoregulation and requiring an intact permease transporter domain.
abstract: The nematode Caenorhabditis elegans has retained a rudimentary Hedgehog (Hh) signalling pathway; Hh and Smoothened (Smo) homologs are absent, but two highly related Patched gene homologs, ptc-1 and ptc-3, and 24 ptc-related (ptr) genes are present. We previously showed that ptc-1 is essential for germ line cytokinesis. Here, we report that ptc-3 is also an essential gene; the absence of ptc-3 results in a late embryonic lethality due to an apparent defect in osmoregulation. Rescue of a ptc-3 mutant with a ptc-3::gfp translational reporter reveals that ptc-3 is dynamically expressed in multiple tissues across development. Consistent with this pattern of expression, ptc-3(RNAi) reveals an additional postembryonic requirement for ptc-3 activity. Tissue-specific promoter studies indicate that hypodermal expression of ptc-3 is required for normal development. Missense changes in key residues of the sterol sensing domain (SSD) and the permease transporter domain GxxxD/E motif reveal that the transporter domain is essential for PTC-3 activity, whereas an intact SSD is dispensable. Taken together, our studies indicate that PTC proteins have retained essential roles in C. elegans that are independent of Smoothened (Smo). These observations reveal novel, and perhaps ancestral, roles for PTC proteins.
authors.affiliation: University of Bristol, School of Biochemistry, Bristol, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Soloviev
authors.forename: Joseph
authors.initials: J
authors.lastname: Gallagher
authors.forename: Aline
authors.initials: A
authors.lastname: Marnef
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Kuwabara
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D018507:Gene Expression Regulation, Developmental; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014882:Water-Electrolyte Balance
chemical_list: D029742:Caenorhabditis elegans Proteins; D026901:Membrane Transport Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; C000606244:ptc-1 protein, C elegans