Abstract
The cystic kidney diseases nephronophthisis (NPHP), Meckel–Gruber syndrome (MKS) and Joubert syndrome (JBTS) share an underlying etiology of dysfunctional cilia. Patients diagnosed with NPHP type II have mutations in the gene
INVS
(also known as
NPHP2
), which encodes inversin, a cilia localizing protein. Here, we show that the
C. elegans
inversin ortholog, NPHP-2, localizes to the middle segment of sensory cilia and that
nphp-2
is partially redundant with
nphp-1
and
nphp-4
(orthologs of human
NPHP1
and
NPHP4
, respectively) for cilia placement within the head and tail sensilla.
nphp-2
also genetically interacts with MKS ciliopathy gene orthologs, including
mks-1, mks-3, mks-6, mksr-1
and
mksr-2
, in a sensilla-dependent manner to control cilia formation and placement. However,
nphp-2
is not required for correct localization of the NPHP- and MKS-encoded ciliary transition zone proteins or for intraflagellar transport (IFT). We conclude that
INVS
/
NPHP2
is conserved in
C. elegans
and that
nphp-2
plays an important role in
C. elegans
cilia by acting as a modifier of the NPHP and MKS pathways to control cilia formation and development.