HNF-1beta regulates transcription of the PKD modifier gene Kif12.

Hepatocyte nuclear factor-1beta (HNF-1beta) is a transcription factor that regulates gene expression in the kidney, liver, pancreas, and other epithelial organs. Mutations of HNF-1beta lead to a syndrome of inherited renal cysts and diabetes and are also a common cause of sporadic renal dysplasia. The full complement of target genes responsible for the functions of HNF-1beta, however, is incompletely defined.

Mutations of HNF-1beta inhibit epithelial morphogenesis through dysregulation of SOCS-3.

Hepatocyte nuclear factor-1beta (HNF-1beta) is a Pit-1, Oct-1/2, Unc-86 (POU) homeodomain-containing transcription factor expressed in the kidney, liver, pancreas, and other epithelial organs. Mutations of HNF-1beta cause maturity-onset diabetes of the young, type 5 (MODY5), which is characterized by early-onset diabetes mellitus and congenital malformations of the kidney, pancreas, and genital tract. Knockout of HNF-1beta in the mouse kidney results in cyst formation.

The role for HNF-1beta-targeted collectrin in maintenance of primary cilia and cell polarity in collecting duct cells.

Collectrin, a homologue of angiotensin converting enzyme 2 (ACE2), is a type I transmembrane protein, and we originally reported its localization to the cytoplasm and apical membrane of collecting duct cells. Recently, two independent studies of targeted disruption of collectrin in mice resulted in severe and general defects in renal amino acid uptake. Collectrin has been reported to be under the transcriptional regulation by HNF-1alpha, which is exclusively expressed in proximal tubules and localized at the luminal side of brush border membranes.

Proteolytic cleavage and nuclear translocation of fibrocystin is regulated by intracellular Ca2+ and activation of protein kinase C.

Fibrocystin, a type I membrane protein of unknown function, is the protein affected in the autosomal recessive form of polycystic kidney disease. Here we show that fibrocystin undergoes regulated proteolysis. Several proteolytic cleavages occur within the predicted ectodomain, whereas at least one cleavage occurs within the cytoplasmic portion.

Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain development.

Targeted deletion of two members of the FE65 family of adaptor proteins, FE65 and FE65L1, results in cortical dysplasia. Heterotopias resembling those found in cobblestone lissencephalies in which neuroepithelial cells migrate into superficial layers of the developing cortex, aberrant cortical projections and loss of infrapyramidal mossy fibers arise in FE65/FE65L1 compound null animals, but not in single gene knockouts. The disruption of pial basal membranes underlying the heterotopias and poor organization of fibrillar laminin by isolated meningeal fibroblasts from double knockouts suggests that FE65 proteins are involved in basement membrane assembly.