title: aPKCλ/ι and aPKCζ contribute to podocyte differentiation and glomerular maturation.
abstract: Precise positioning of the highly complex interdigitating podocyte foot processes is critical to form the normal glomerular filtration barrier, but the molecular programs driving this process are unknown. The protein atypical protein kinase C (aPKC)--a component of the Par complex, which localizes to tight junctions and interacts with slit diaphragm proteins--may play a role. Here, we found that the combined deletion of the aPKCλ/ι and aPKCζ isoforms in podocytes associated with incorrectly positioned centrosomes and Golgi apparatus and mislocalized molecules of the slit diaphragm. Furthermore, aPKC-deficient podocytes failed to form the normal network of foot processes, leading to defective glomerular maturation with incomplete capillary formation and mesangiolysis. Our results suggest that aPKC isoforms orchestrate the formation of the podocyte processes essential for normal glomerular development and kidney function. Defective aPKC signaling results in a dramatically simplified glomerular architecture, causing severe proteinuria and perinatal death.
authors: Renal Division, University Hospital Freiburg, Freiburg, Germany.
authors: Björn
authors: B
authors: Hartleben
authors: Eugen
authors: E
authors: Widmeier
authors: Martina
authors: M
authors: Suhm
authors: Kirstin
authors: K
authors: Worthmann
authors: Christoph
authors: C
authors: Schell
authors: Martin
authors: M
authors: Helmstädter
authors: Thorsten
authors: T
authors: Wiech
authors: Gerd
authors: G
authors: Walz
authors: Michael
authors: M
authors: Leitges
authors: Mario
authors: M
authors: Schiffer
authors: Tobias B
authors: TB
authors: Huber
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002454:Cell Differentiation / Q000502:physiology; D018385:Centrosome / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006056:Golgi Apparatus / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000166:cytology / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D050199:Podocytes / Q000201:enzymology* / Q000473:pathology* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D019108:Tight Junctions / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta