PgmNr W4171: Caenorhabditis elegans extracellular matrix proteins regulate polycystin localization/activity and cilia integrity.

Authors:
Deanna Michele De Vore; Maureen Barr


Institutes
Rutgers University, Piscataway, NJ.


Keyword: Other ( Extracellular matrix )

Abstract:

PKD2 encodes a transient receptor potential polycystin (TRPP) channel receptor protein found in primary cilia of mammalian cells and sensory cilia of C. elegans neurons. In humans, PKD2 mutations result in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Given the ancient and evolutionarily conserved role for polycystin-2 in cilia, we are using C. elegans as a model to identify new genes required for ciliary receptor localization. We recently found that extracellular matrix components are important for C. elegans PKD2 localization and function. ECM formation, secretion, and integrity have been shown to be a primary factor in ADPKD (Mangos 2010). Transmembrane and ECM proteins such as cadherins and galectins act in cilium retraction and elongation and also play a role in cell-to-cell junction signaling via the ECM (Seeger 2012, Rondanino 2011). 

mec-1, mec-5, and mec-9 encode ECM components that play a role in mechanosensation and degenerin/epithelial sodium channel (DEG/ENaCs) localization in non-ciliated touch receptor neurons (Du 1996, Emtage 2004).  mec-1 and mec-9 encode proteins with multiple EGF and Kunitz domains; mec-5 encodes a collagen (Du1996, Emtage 2004). I found that the ECM encoding genes mec-1, mec-5, and mec-9  also regulate polycystin localization in male-specific ciliated sensory neurons.  I further show that these proteins regulate mating behaviors and cilia structure. I am currently exploring their roles in localization of other ciliary proteins and determining the mechanisms by which these ECM proteins.  This study may provide insight on how extracellular matrix proteins contribute to ciliary localization of sensory receptors like PKD-2, and advance the understanding and expand the options for treatment of ciliopathies such as ADPKD.  .



Wormbase Genetic Index
1. pkd-2
2. lov-1
3. mec-1
4. mec-9
5. mec-5