Mapping the CPLANE interactome, an extensive protein interaction network underlying human ciliopathies

NIH RePORTER · NIH · R01 · $509,504 · view on reporter.nih.gov ↗

Abstract

ABSTRACT Cilia are essential organelles, with functions ranging from cell-cell signaling to the generation of homeostatic fluid flow in tubular organs. Consequently, an array of human congenital diseases has been characterized as “ciliopathies,” because they share an etiology of defective cilia structure or function. Despite manifest roles in the disruption of the central nervous system, limbs, axial skeleton, kidneys, airway, brain, and reproductive tracts, our understanding of the mechanisms that govern ciliogenesis and cilia-mediated developmental patterning remain incomplete. We propose here to study the roles of a novel multi-protein complex that controls three crucial mechanisms: basal body docking, IntraFlagellar Transport (IFT) recruitment, and Planar Cell Polarity (PCP). We will do so using a combination of proteomics, in vivo cell biology, mouse genetics and human disease modeling. By focusing on proteins with demonstrated importance in development and disease, but for which no mechanism of action is yet known, experiments proposed here will provide important new breadth and depth to our understanding cilia-mediated developmental patterning, basal body docking, and novel cell biological processes in ciliary biology. In turn, these findings should provide greater insight to a range of congenital diseases including both the relatively mild Oral-Facial-Digital syndrome and the wholly lethal Short Rib Polydactyly.

Key facts

NIH application ID
9962434
Project number
5R01HD085901-05
Recipient
UNIVERSITY OF TEXAS AT AUSTIN
Principal Investigator
EDWARD M MARCOTTE
Activity code
R01
Funding institute
NIH
Fiscal year
2020
Award amount
$509,504
Award type
5
Project period
2016-09-05 → 2021-06-30