Phospholipase C-?? gene of the spontaneously hypertensive rat harbors point mutations causing amino acid substitutions in a catalytic domain

Yagisawa, Hitoshi; Tanase, Hisao; Nishimura, Hiroshi

doi:10.1097/00004872-199111000-00004

Cited by 33 publications

(14 citation statements)

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“…However, mouse sperm need PIC␦4 to initiate the acrosome reaction and achieve efficient fertilization (56), and spore germination is aberrant in Dictyostelium that lack this organism's only PIC␦ (57). Moreover, PLC␦1 accumulates abnormally in the neurofibrillary tangles of Alzheimer's disease (58,59) and in brain subjected to hyperoxic stress (60) or aluminum toxicity (61), and Alzheimer's patients and spontaneously hypertensive rats harbor unusual PLC␦1 alleles (62)(63)(64).…”

Section: Discussionmentioning

confidence: 99%

Hypo-osmotic Stress Activates Plc1p-dependent Phosphatidylinositol 4,5-Bisphosphate Hydrolysis and Inositol Hexakisphosphate Accumulation in Yeast

Perera

Michell

Dove

2004

Journal of Biological Chemistry

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Polyphosphoinositide-specific phospholipases (PICs) of the ␦-subfamily are ubiquitous in eukaryotes, but an inability to control these enzymes physiologically has been a major obstacle to understanding their cellular function(s). Plc1p is similar to metazoan ␦-PICs and is the only PIC in Saccharomyces cerevisiae. Genetic studies have implicated Plc1p in several cell functions, both nuclear and cytoplasmic. Here we show that a brief hypo-osmotic episode provokes rapid Plc1p-catalyzed hydrolysis of PtdIns(4,5)P 2 in intact yeast by a mechanism independent of extracellular Ca 2؉ . Much of this PtdIns(4,5)P 2 hydrolysis occurs at the plasma membrane. The hydrolyzed PtdIns(4,5)P 2 is mainly derived from PtdIns4P made by the PtdIns 4-kinase Stt4p. PtdIns(4,5)P 2 hydrolysis occurs normally in mutants lacking Arg82p or Ipk1p, but they accumulate no InsP 6 , showing that these enzymes normally convert the liberated Ins(1,4,5)P 3 rapidly and quantitatively to InsP 6 . We conclude that hypo-osmotic stress activates Plc1p-catalyzed PtdIns(4,5)P 2 at the yeast plasma membrane and the liberated Ins(1,4,5)P 3 is speedily converted to InsP 6 . This ability routinely to activate Plc1p-catalyed PtdIns(4,5)P 2 hydrolysis in vivo opens up new opportunities for molecular and genetic scrutiny of the regulation and functions of phosphoinositidases C of the ␦-subfamily.

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Section: Discussionmentioning

confidence: 99%

Hypo-osmotic Stress Activates Plc1p-dependent Phosphatidylinositol 4,5-Bisphosphate Hydrolysis and Inositol Hexakisphosphate Accumulation in Yeast

Perera

Michell

Dove

2004

Journal of Biological Chemistry

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“…In the spontaneously hypertensive rat, a variation in PLC-␦1 sequence was reported, but its involvement in the function remains unclear. 21 The site of the 864G-A variant corresponds to the fourth lobe of the EF hand domain of PLC-␦1. Nakashima et al 22 reported that the EF hand domain may not play a role in the regulation of Ca 2ϩ sensitivity of PLC-␦1.…”

Section: Nakano Et Al Phospholipase C-␦1 Variant In Coronary Spasm 2027mentioning

confidence: 99%

Enhanced Activity of Variant Phospholipase C-δ1 Protein (R257H) Detected in Patients With Coronary Artery Spasm

et al. 2002

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Background-We recently demonstrated that phospholipase C (PLC)-␦1 activity in cultured skin fibroblasts obtained from patients with coronary spastic angina (CSA) is enhanced. We tested the hypothesis that structural abnormality in PLC-␦1 isoform is a cause of the enhanced activity. Methods and Results-Sequence analysis of the cDNA coding for PLC-␦1 obtained from fibroblasts revealed that one conversion of guanine to adenine (A) was present at nucleotide position 864 in one CSA patient, resulting in the amino acid replacement of arginine 257 by histidine (R257H). The incidence of 864A/A in genomic DNA, analyzed by single-strand conformation polymorphism, was greater in patients with CSA than in male control subjects (6 of 57 patients with CSA versus 1 of 62 control subjects, PϽ0.05). The activity of the variant PLC-␦1 protein under free calcium concentration between 10 Ϫ8 and 10 Ϫ7 mol/L was 2-fold higher than that of the wild-type protein. Baseline intracellular calcium concentration ([Ca 2ϩ ] i ) in human embryonic kidney 293 cells transfected with the variant PLC-␦1 was higher than that in cells with the wild type. The peak increase in [Ca 2ϩ ] i in response to acetylcholine at 10 Ϫ6 and 10 Ϫ5 mol/L was greater in the cells with the variant PLC-␦1 than in those with the wild type. Conclusions-These findings indicate that the R257H variant in the PLC-␦1 gene detected in patients with CSA is associated with enhancement of enzyme activity, and they describe a novel mechanism for the enhanced coronary vasomotility in

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“…Multiple allelic polymorphisms of phospholipase C isozyme genes have been detected in SHR compared with WKY rats, 4041 but only one polymorphism in the phospholipase C-S gene appears to be specific for genetic forms of hypertension. Although this polymorphism encodes a point mutation in the catalytic domain of the enzyme, 41 it is not clear whether this yields altered enzymatic activity. In fact, a recent breeding study demonstrated that the SHR allele of phospholipase C-5 cosegregates with low rather than with high blood pressure in an F 2 population of WKY x SHR hybrid rats.…”

Section: Fig 6 Line Graphs Show Development Of Basal and Isoproterenmentioning

confidence: 99%

Ontogenesis of sympathetic responsiveness in spontaneously hypertensive rats. I. Renal alpha 1-, alpha 2-, and beta-adrenergic receptors and their signaling.

et al. 1993

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We studied the ontogenetic development of renal t v , o^-, and /3-adrenergic receptors and their coupling to inositol phosphate and cyclic AMP formation in spontaneously hypertensive and normotensive Wistar-Kyoto rats, a,-, <%-, and /3-Adrenergic receptor number was significantly increased in hypertensive compared with normotensive rats, but the increase did not precede blood pressure elevation. Despite increased a,-adrenergic receptors, basal and norepinephrine-stimulated inositol phosphate formation remained unchanged in all age groups. Rat kidney contains a, A -and «, B -adrenergic receptors coupling to inositol phosphate formation by different mechanisms, but the relative contribution of «, A -and ff, B -adrenergic receptors to norepinephrine-stimulated inositol phosphate formation was similar in normotensive and hypertensive rats. Despite increased /3-adrenergic receptors, basal, isoproterenol-, and forskolin-stimulated cyclic AMP accumulation was similar in normotensive and hypertensive rats. We conclude that the number but not the functional responsiveness of renal adrenergic receptors increases in spontaneously hypertensive rats. Thus, the additional receptors are unlikely to contribute to the pathophysiology of elevated blood pressure in this model.

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Phospholipase C-?? gene of the spontaneously hypertensive rat harbors point mutations causing amino acid substitutions in a catalytic domain

Cited by 33 publications

References 0 publications

Hypo-osmotic Stress Activates Plc1p-dependent Phosphatidylinositol 4,5-Bisphosphate Hydrolysis and Inositol Hexakisphosphate Accumulation in Yeast

Hypo-osmotic Stress Activates Plc1p-dependent Phosphatidylinositol 4,5-Bisphosphate Hydrolysis and Inositol Hexakisphosphate Accumulation in Yeast

Enhanced Activity of Variant Phospholipase C-δ1 Protein (R257H) Detected in Patients With Coronary Artery Spasm

Ontogenesis of sympathetic responsiveness in spontaneously hypertensive rats. I. Renal alpha 1-, alpha 2-, and beta-adrenergic receptors and their signaling.

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