Journal of Inherited Metabolic Disease

, Volume 32, Issue 2, pp 280–288

Abnormal bradykinin signalling in fibroblasts deficient in the PIP2 5-phosphatase, ocrl1

Authors

    • Genetic Disease Research Branch, National Human Genome Research InstituteNational Institutes of Health
    • GeneDx
  • J. C. Cronin
    • Genetic Disease Research Branch, National Human Genome Research InstituteNational Institutes of Health
  • R. L. Nussbaum
    • Genetic Disease Research Branch, National Human Genome Research InstituteNational Institutes of Health
    • Institute for Human Genetics and Division of Medical Genetics, Department of MedicineUniversity of California, San Francisco
Original Article

DOI: 10.1007/s10545-009-1058-3

Cite this article as:
Suchy, S.F., Cronin, J.C. & Nussbaum, R.L. J Inherit Metab Dis (2009) 32: 280. doi:10.1007/s10545-009-1058-3

Summary

The oculocerebrorenal syndrome of Lowe (Lowe syndrome) is an X-linked disorder of phosphatidylinositol metabolism characterized by congenital cataracts, renal proximal tubulopathy and neurological deficits. The disorder is due to the deficiency of the phosphatidylinositol 4,5-bisphosphate (PIP2) 5-phosphatase, ocrl1. PIP2 is critical for numerous cellular processes, including cell signalling, actin reorganization and protein trafficking, and is chronically elevated in patients with Lowe syndrome. The elevation of PIP2 cells of patients with Lowe syndrome provides the unique opportunity to investigate the roles of this phospholipid in fundamental cellular processes. We previously demonstrated that ocrl1 deficiency causes alterations in the actin cytoskeleton. Since actin remodelling is strongly activated by [Ca+2], which increases in response to IP3 production, we hypothesized that altered calcium signalling might contribute to the observed abnormalities in actin organization. Here we report a specific increase in bradykinin-induced Ca+2 mobilization in Lowe fibroblasts. We show that the abnormal bradykinin signalling occurs in spite of normal total cellular receptor content. These data point to a novel role for ocrl1 in agonist-induced calcium release.

Abbreviations

2-APB

2-aminoethoxydiphenylborate

EGF

epidermal growth factor

GPCR

G-protein-coupled receptor

PDGF

platelet-derived growth factor

PIP2

phosphatidylinositol 4,5-bisphosphate

TGN

trans-Golgi network

Copyright information

© Springer Science+Business Media B.V. 2009