LOWE-SYNDROME, A DEFICIENCY OF A PHOSPHATIDYL-INOSITOL 4,5-BISPHOSPHATE 5-PHOSPHATASE IN THE GOLGI-APPARATUS
LOWE-SYNDROME, A DEFICIENCY OF A PHOSPHATIDYL-INOSITOL 4,5-BISPHOSPHATE 5-PHOSPHATASE IN THE GOLGI-APPARATUS
复制标题
DOI：
10.1093/hmg/4.12.2245
复制
发表时间：
1995-12-01
影响因子：
3.5
通讯作者：
NUSSBAUM, RL
中科院分区：
文献类型：
--
作者：
SUCHY, SF;OLIVOSGLANDER, IM;NUSSBAUM, RL
The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, renal tubular dysfunction and neurological deficits, The gene responsible for this disorder, OCRL-1, has been cloned and mutations identified in patients. The gene product (ocrl-1) has extensive sequence homology to a 75 kDa inositol polyphosphate 5-phosphatase. We report here that OCRL patients' fibroblasts show no abnormality in inositol polyphosphate 5-phosphatase activity, but are deficient in a phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2] 5-phosphatase activity localized to the Golgi apparatus, Direct biochemical diagnosis of this human disease should now be possible. PtdIns(4,5)P-2 has been implicated in Golgi vesicular transport through its role in the regulation of ADP-ribosylation factor, phospholipase D and actin assembly in the cytoskeleton, The regulation of PtdIns(4,5)P-2 levels by PtdIns(4,5)P-2 5-phosphatase may, therefore, be important in the modulation of Golgi vesicular transport, Given that the primary defect in OCRL is a deficiency of a Golgi PtdIns(4,5)P-2 phosphatase, we hypothesize that the disorder results from dysregulation of Golgi function and in this way causes developmental defects in the lens and abnormal renal and neurological function.
