The role of phospholipase C isozymes in cellular homeostasis

Kiyoko Fukami; Yoshikazu Nakamura

doi:10.1007/978-1-4939-0464-8_12

The role of phospholipase C isozymes in cellular homeostasis

Kiyoko Fukami, Yoshikazu Nakamura

Department of Applied Biological Science

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

Abstract

Phosphoinositide turnover influences various functions such as cell proliferation/differentiation, fertilization, neuronal functions, and cell motility. Phospholipase C (PLC) triggers the hydrolysis of phosphatidylinositol 4.5- bisphosphate (PI(4,5)P₂) to generate two second messengers, inositol 1.4.5-strisphosphate (Ins(1,4,5)P3), and diacylglycerol (DAG). Ins(1,4,5)P3 releases calcium from intracellular stores, and DAG activates protein kinase C (PKC). PI(4,5)P2 also directly regulates various cellular functions, including cytoskeletal remodeling, endocytosis/exocytosis, and channel activity. Imbalances in these phos- phoinositides facilitate the pathogenesis of various human diseases. Therefore, precise regulation of the levels of PI(4,5)P₂ by PLC or other interconverting enzymes is indispensable for normal cellular functions. Recently several mouse models with genetic-deficits of PLC isozymes have been generated and these analyses revealed the specific functions of each of these isozymes. Taken together with the genome- based information, specific isozymes were found to have a pivotal role in maintaining cellular homeostasis. Since PLC is an intracellular calcium-regulating enzyme, the PLC knockout (KO) mice often show disruption in the calcium homeostasis. This article reviews the regulation of calcium homeostasis by PLC isozymes in fertilization and neuronal functions. PLCKO mice have abnormal cellular proliferation, differentiation, apoptosis, and development, suggesting that PLC isozyme facilitates the determination of cell fate. These physiological regulations are implicated in several cellular functions and play a very important role, especially in tissues with high metabolic turnover such as the skin, colon, hematopoietic cells, and developing embryo. Therefore, the focus of this review is on the physiological functions of PLC isozymes in these cells and on the diseases that are caused by the dysregulation of PLC isozymes and consequent disruption in calcium- and cellular-homeostasis.

Original language	English
Title of host publication	Phospholipases in Health and Disease
Publisher	Springer New York
Pages	201-210
Number of pages	10
Volume	10
ISBN (Electronic)	9781493904648
ISBN (Print)	9781493904631
DOIs	https://doi.org/10.1007/978-1-4939-0464-8_12
Publication status	Published - 1 Jan 2014

Keywords

Calcium
Cell growth
Differentiation
Homeostasis
Phospholipase C
Skin
Tumorigenesis

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10.1007/978-1-4939-0464-8_12

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title = "The role of phospholipase C isozymes in cellular homeostasis",

abstract = "Phosphoinositide turnover influences various functions such as cell proliferation/differentiation, fertilization, neuronal functions, and cell motility. Phospholipase C (PLC) triggers the hydrolysis of phosphatidylinositol 4.5- bisphosphate (PI(4,5)P2) to generate two second messengers, inositol 1.4.5-strisphosphate (Ins(1,4,5)P3), and diacylglycerol (DAG). Ins(1,4,5)P3 releases calcium from intracellular stores, and DAG activates protein kinase C (PKC). PI(4,5)P2 also directly regulates various cellular functions, including cytoskeletal remodeling, endocytosis/exocytosis, and channel activity. Imbalances in these phos- phoinositides facilitate the pathogenesis of various human diseases. Therefore, precise regulation of the levels of PI(4,5)P2 by PLC or other interconverting enzymes is indispensable for normal cellular functions. Recently several mouse models with genetic-deficits of PLC isozymes have been generated and these analyses revealed the specific functions of each of these isozymes. Taken together with the genome- based information, specific isozymes were found to have a pivotal role in maintaining cellular homeostasis. Since PLC is an intracellular calcium-regulating enzyme, the PLC knockout (KO) mice often show disruption in the calcium homeostasis. This article reviews the regulation of calcium homeostasis by PLC isozymes in fertilization and neuronal functions. PLCKO mice have abnormal cellular proliferation, differentiation, apoptosis, and development, suggesting that PLC isozyme facilitates the determination of cell fate. These physiological regulations are implicated in several cellular functions and play a very important role, especially in tissues with high metabolic turnover such as the skin, colon, hematopoietic cells, and developing embryo. Therefore, the focus of this review is on the physiological functions of PLC isozymes in these cells and on the diseases that are caused by the dysregulation of PLC isozymes and consequent disruption in calcium- and cellular-homeostasis.",

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AU - Nakamura, Yoshikazu

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N2 - Phosphoinositide turnover influences various functions such as cell proliferation/differentiation, fertilization, neuronal functions, and cell motility. Phospholipase C (PLC) triggers the hydrolysis of phosphatidylinositol 4.5- bisphosphate (PI(4,5)P2) to generate two second messengers, inositol 1.4.5-strisphosphate (Ins(1,4,5)P3), and diacylglycerol (DAG). Ins(1,4,5)P3 releases calcium from intracellular stores, and DAG activates protein kinase C (PKC). PI(4,5)P2 also directly regulates various cellular functions, including cytoskeletal remodeling, endocytosis/exocytosis, and channel activity. Imbalances in these phos- phoinositides facilitate the pathogenesis of various human diseases. Therefore, precise regulation of the levels of PI(4,5)P2 by PLC or other interconverting enzymes is indispensable for normal cellular functions. Recently several mouse models with genetic-deficits of PLC isozymes have been generated and these analyses revealed the specific functions of each of these isozymes. Taken together with the genome- based information, specific isozymes were found to have a pivotal role in maintaining cellular homeostasis. Since PLC is an intracellular calcium-regulating enzyme, the PLC knockout (KO) mice often show disruption in the calcium homeostasis. This article reviews the regulation of calcium homeostasis by PLC isozymes in fertilization and neuronal functions. PLCKO mice have abnormal cellular proliferation, differentiation, apoptosis, and development, suggesting that PLC isozyme facilitates the determination of cell fate. These physiological regulations are implicated in several cellular functions and play a very important role, especially in tissues with high metabolic turnover such as the skin, colon, hematopoietic cells, and developing embryo. Therefore, the focus of this review is on the physiological functions of PLC isozymes in these cells and on the diseases that are caused by the dysregulation of PLC isozymes and consequent disruption in calcium- and cellular-homeostasis.

AB - Phosphoinositide turnover influences various functions such as cell proliferation/differentiation, fertilization, neuronal functions, and cell motility. Phospholipase C (PLC) triggers the hydrolysis of phosphatidylinositol 4.5- bisphosphate (PI(4,5)P2) to generate two second messengers, inositol 1.4.5-strisphosphate (Ins(1,4,5)P3), and diacylglycerol (DAG). Ins(1,4,5)P3 releases calcium from intracellular stores, and DAG activates protein kinase C (PKC). PI(4,5)P2 also directly regulates various cellular functions, including cytoskeletal remodeling, endocytosis/exocytosis, and channel activity. Imbalances in these phos- phoinositides facilitate the pathogenesis of various human diseases. Therefore, precise regulation of the levels of PI(4,5)P2 by PLC or other interconverting enzymes is indispensable for normal cellular functions. Recently several mouse models with genetic-deficits of PLC isozymes have been generated and these analyses revealed the specific functions of each of these isozymes. Taken together with the genome- based information, specific isozymes were found to have a pivotal role in maintaining cellular homeostasis. Since PLC is an intracellular calcium-regulating enzyme, the PLC knockout (KO) mice often show disruption in the calcium homeostasis. This article reviews the regulation of calcium homeostasis by PLC isozymes in fertilization and neuronal functions. PLCKO mice have abnormal cellular proliferation, differentiation, apoptosis, and development, suggesting that PLC isozyme facilitates the determination of cell fate. These physiological regulations are implicated in several cellular functions and play a very important role, especially in tissues with high metabolic turnover such as the skin, colon, hematopoietic cells, and developing embryo. Therefore, the focus of this review is on the physiological functions of PLC isozymes in these cells and on the diseases that are caused by the dysregulation of PLC isozymes and consequent disruption in calcium- and cellular-homeostasis.

KW - Calcium

KW - Cell growth

KW - Differentiation

KW - Homeostasis

KW - Phospholipase C

KW - Skin

KW - Tumorigenesis

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DO - 10.1007/978-1-4939-0464-8_12

M3 - Chapter

AN - SCOPUS:85028626687

SN - 9781493904631

VL - 10

SP - 201

EP - 210

BT - Phospholipases in Health and Disease

PB - Springer New York

ER -

The role of phospholipase C isozymes in cellular homeostasis

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Keywords

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