Podocin Explained

Podocin is a protein component of the filtration slits of podocytes. Glomerular capillary endothelial cells, the glomerular basement membrane and the filtration slits function as the filtration barrier of the kidney glomerulus.^[1] Mutations in the podocin gene NPHS2 can cause nephrotic syndrome, such as focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD).^[2] Symptoms may develop in the first few months of life (congenital nephrotic syndrome) or later in childhood.^[3]

Structure

Podocin is a membrane protein of the band-7-stomatin family, consisting of 383 amino acids. It has a transmembrane domain forming a hairpin structure, with two cytoplasmic ends at the N- and C-terminus, the latter of which interacts with the cytosolic tail of nephrin, with CD2AP serving as an adaptor.^[4]

Function

Podocin is localized on the membranes of podocyte pedicels (foot-like long processes), where it oligomerizes in lipid rafts together with nephrin to form the filtration slits.

Notes and References

1. Jarad G, Miner JH . Update on the glomerular filtration barrier . Current Opinion in Nephrology and Hypertension . 18 . 3 . 226–32 . May 2009 . 19374010 . 2895306 . 10.1097/mnh.0b013e3283296044 .
2. Mollet G, Ratelade J, Boyer O, Muda AO, Morisset L, Lavin TA, Kitzis D, Dallman MJ, Bugeon L, Hubner N, Gubler MC, Antignac C, Esquivel EL . Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome . Journal of the American Society of Nephrology . 20 . 10 . 2181–9 . October 2009 . 19713307 . 2754108 . 10.1681/ASN.2009040379 .
3. Book: Pediatric Nephrology. Ellis D . Avner . William E . Harmon . Patrick . Niaudet . Norishige . Yoshikawa . Francesco . Emma . Stuart L . Goldstein . vanc . 2016 . Springer . 9783662435960 . 1050008865.
4. Tabassum A, Rajeshwari T, Soni N, Raju DS, Yadav M, Nayarisseri A, Jahan P . Structural characterization and mutational assessment of podocin - a novel drug target to nephrotic syndrome - an in silico approach . Interdisciplinary Sciences, Computational Life Sciences . 6 . 1 . 32–9 . March 2014 . 24464702 . 10.1007/s12539-014-0190-4 . 17163784 .