Arif, Ehtesham and Mallik, Leena and Rathore, Yogendra S and Kumari, Babita and Ostap, Michael and Ashish, . and Holzman, Lawrence B and Nihalani, Deepak (2013) Myo1c, an unconventional motor that maintains glomerular filtration function. FASEB Journal, 27.
Full text not available from this repository. (Request a copy)Abstract
Podocytes and their specialized junctions "slit diaphragm" are key components of glomerular filtration system and their dysfunction is associated with impaired kidney function. We recently demonstrated that motor protein Myo1c mediates translocation of slit diaphragm proteins Neph1 and Nephrin from cytoplasm to podocytes cell membrane that is critical for renal function. In this study, we investigated physiological significance of Myo1c in maintaining glomerular filtration barrier using zebrafish as a model system. In addition, we performed structural and biochemical experiments to decipher the interacting regions in Myo1c and Neph1 that provides mechanistic insight into the assembly of Neph1 and its complexes at podocyte membrane. Knockdown of Myo1c in zebrafish using morpholinos impaired the glomerular filtration function. The solution structures of full length Myo1c in complex with the cytoplasmic domain of Neph1 was resolved using small/wide angle X-ray scattering. The structural analysis revealed multiple regions in Myo1c and Neph1 that mediate this interaction. Binding mutants derived from this analysis confirmed the validity of this approach and the imaging experiments further demonstrated the inability of these mutants to localize at podocyte cell membrane and rescue a renal phenotype in zebrafish Neph1 knockdown model. Collectively, these results support a critical role for Myo1c in renal physiology.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to Federation of American Societies for Experimental Biology. |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 10 Feb 2015 11:00 |
| Last Modified: | 04 Sep 2019 09:08 |
| URI: | http://crdd.osdd.net/open/id/eprint/1597 |
Actions (login required)
 |
View Item |
