[Frontiers In Bioscience, Landmark, 22, 1330-1343, March 1, 2017]

The mucolipin-1 (TRPML1) ion channel, transmembrane-163 (TMEM163) protein, and lysosomal zinc handling

Math P. Cuajungco1,2, Kirill Kiselyov3

1Department of Biological Science, and 2Center for Applied Biotechnology Studies, California State University Fullerton, Fullerton, CA, 92831, USA, 3Department of Biological Sciences, University of Pittsburgh, PA, 15260, USA


1. Abstract
2. Introduction
3. The lysosomal zinc sink
4. TMEM163 and zinc accumulation
5. Acknowledgments
6. References


Lysosomes are emerging as important players in cellular zinc ion (Zn2+) homeostasis. The series of work on Zn2+ accumulation in the neuronal lysosomes and the mounting evidence on the role of lysosomal Zn2+ in cell death during mammary gland involution set a biological precedent for the central role of the lysosomes in cellular Zn2+ handling. Such a role appears to involve cytoprotection on the one hand, and cell death on the other. The recent series of work began to identify the molecular determinants of the lysosomal Zn2+ handling. In addition to zinc transporters (ZnT) of the solute-carrier family type 30A (SLC30A), the lysosomal ion channel TRPML1 and the poorly understood novel transporter TMEM163 have been shown to play a role in the Zn2+ uptake by the lysosomes. In this review, we summarize the current knowledge on molecular determinants of the lysosomal Zn2+ handling, uptake, and release pathways, as well as discuss their possible roles in health and disease.


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Key Words: Mucolipidosis IV, lysosomes, zinc transport, SV31, Review

Send correspondence to: Kirill Kiselyov, Dept. of Biological Sciences, University of Pittsburgh, 519 Langley Hall, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA, Tel: 412-624-4317, Fax: 412-624-4759, E-mail: kiselyov@pitt.edu