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The Role of Phospholipase C Isozymes in Cellular Homeostasis

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Phospholipases in Health and Disease

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 10))

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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-trisphosphate (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 phosphoinositides 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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Authors and Affiliations

  1. Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, 192-0392, Tokyo, Japan

    Kiyoko Fukami & Yoshikazu Nakamura

Authors
  1. Kiyoko Fukami
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  2. Yoshikazu Nakamura
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Correspondence to Kiyoko Fukami .

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Editors and Affiliations

  1. I.H. Asper Clinical Research Institute St. Boniface Hospital Research, Winnipeg, Manitoba, Canada

    Paramjit S. Tappia

  2. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

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Fukami, K., Nakamura, Y. (2014). The Role of Phospholipase C Isozymes in Cellular Homeostasis. In: Tappia, P., Dhalla, N. (eds) Phospholipases in Health and Disease. Advances in Biochemistry in Health and Disease, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0464-8_12

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