Our research is focused on defining the cellular functions and molecular interactions of fleer; a gene that we identified in zebrafish by positional cloning.
Narendra H. Pathak, PhD
Instructor of Medicine
149 13th Street
Charlestown, MA 02129
Phone: (617) 724-8897
Fax: (617) 726-5669
Our research is focused on defining the cellular functions and molecular interactions of fleer; a gene that we identified in zebrafish by positional cloning. The pleotropic phenotype of the zebrafish fleer mutant resembles human ciliopathies and involves pronephric cysts, axis curvature, and retinal degeneration. Fleer encodes a tetratricopeptide (TPR) repeat containing cilia protein related to CeDYF-1. Diverse ciliated tissues express fleer and its transcript levels are particularly high in multiciliated cells. Loss of fleer suppresses formation of multicilia, reduces the length and beat amplitude of motile single cilia and induces breaks in the B-tubule of the axonemal outer microtubule doublets. One function of fleer involves regulation of axonemal tubulin glutamylation as zebrafish fleer mutants exhibit tubulin hypoglutamylation in the axonemes of cilia but levels of glutamylated tubulins in their basal bodies and neurons appear normal. Tubulin glutamylation and glycylation are polymeric posttranslational modifications associated with stable microtubules and essential to their structural and functional integrity. Using biochemical approaches and zebrafish genetics, we are currently elaborating the link between fleer and tubulin posttranslational modifications.
- Liu Y, Pathak N, Kramer-Zucker A, and Drummond IA. 2007. Notch-signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros. Development. 134: 1111-1122.
- Pathak N, Obara T, Mangos S, Liu Y, and Drummond IA. 2007. The zebrafish fleer gene encodes an essential regulator of cilia tubulin polyglutamylation. Mol. Biol. Cell. 18: 4353-4364.
- Insinna C, Pathak N, Perkins B, Drummond I, and Besharse JC. 2008. The homodimeric kinesin, Kif17, is essential for vertebrate phtoreceptor sensory outer segment development. Developmental Biology. 316(1): 160-170.