A Model for Polycystic Kidney Disease in C elegans

  • Barr, Maureen (PI)
  • BARR, MAUREEN (PI)
  • BARR, MAUREEN M. (PI)
  • BARR, MAUREEN M. (PI)
  • BARR, MAUREEN M. (PI)
  • BARR, MAUREEN M. (PI)

Project Details

Description

DESCRIPTION (Applicant's Abstract): Autosomal Dominant Polycystic Kidney
Disease (ADPKD) strikes 1 in 1000 individuals, often resulting in end-stage
renal failure. Mutations in either PKD1 or PKD2 account for 95 percent of all
cases. ADPKD1 and ADPKD2 are phenotypically indistinguishable, leading to the
hypothesis that pathology is caused by defects in the same pathway. The
cellular roles of the PKD 1 and PKD2 gene products (polycystin 1 and polycystin
2, respectively) still remain unknown. The powerful molecular genetic tools of
the nematode Caenorhabditis elegans (C. Elegans)will enable us to address
fundamental questions regarding polycystin function and physiological relevance
of partner interactions. The C. elegans homologs of PKD1 and PKD2, LOV-1 and
PKD-2, are coexpressed and colocalized in three types of male chemosensory
neurons: the cephalic CEMs, the HOB hook neuron, and the ray neurons.
Furthermore, lov-1 and pkd-2 are required in the male nervous system for the
mating behaviors of response to hermaphrodite contact and location of the
hermaphrodite vulva (Lov). The C. elegans homolog of Tg737 (a murine gene
associated with Autosomal Recessive PKD) exhibits an expression pattern that
partially overlaps with lov-1 and pkd-2 and maps closely to osm-5. osm-5 is
also necessary for response and Lov behavior, suggesting that the three may
operate in the same cell. This proposal is designed to test the hypothesis that
LOV-1, PKD-2, and possibly CeTg737 act in a common pathway. Experiments will
explore several models of LOV-1, PKD-2, and CeTg737 function. Hypotheses
include the following: CeTg737 may localize LOV-1 and PKD-2 to the cilia where
LOV-1 and PKD-2 are required for function. Moreover, LOV-1 may be involved in
transducing an extracellular signal via PKD-2 in the cilia, culminating in
activation of an intracellular signaling pathway. Alternatively, LOV-1 and
PKD-2 may be involved in the formation and maintenance of sensory cilia or the
establishment and maintenance of neuronal cell polarity. A number of
complementary studies are proposed to address the function of the C. elegans
polycystins and CeTg737 in male mating behavior. Genetic and molecular
interactions between lov-1, pkd-2, and CeTg737 will be explored. Cellular
functions of the C. elegans polycystins will be ascertained. The function of
CeTg737 in male sensory mating behaviors will be determined. New components in
the LOV/PKD pathway will be isolated. These experiments will analyze LOV/PKD at
the cellular, genetic, and molecular levels.
StatusActive
Effective start/end date5/1/016/30/21

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases: $372,116.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $49,624.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $372,639.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $37,487.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $372,116.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $224,236.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $307,218.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $51,261.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $312,925.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $325,081.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $247,350.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $247,350.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $298,434.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $372,116.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $247,350.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $301,389.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $71,558.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $111,099.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $51,261.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $323,475.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $284,996.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $247,350.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $50,133.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $443,674.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $65,959.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $355,224.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $372,116.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $37,487.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $49,624.00

ASJC

  • Medicine(all)
  • Nephrology
  • Psychiatry and Mental health
  • Genetics
  • Physiology
  • Cell Biology
  • Endocrinology, Diabetes and Metabolism

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