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Cellular and molecular function of mucolipins (TRPML) and polycystin 2 (TRPP2)

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Abstract

Mucolipins (transient receptor potential mucolipin, TRPML) and polycystin-2 proteins (transient receptor potential polycystin, TRPP) constitute two small families of cation channels with motif and sequence similarities to the transient receptor potential (TRP) class of non-selective cation channels. Genetic defects in TRPML1 and TRPML3 in humans and in animal models cause the accumulation of large vacuoles, leading to a variety of cellular phenotypes including neurological and neurosensory deficiencies. TRPML1 is a Ca2+-, K+-, and Na+-permeable cation channel sensitive to pH changes, and regulates a critical step in the maturation of late endosomes to lysosomes. Mutations of TRPP2 in humans result in autosomal dominant polycystic kidney disease. Molecular studies have demonstrated that TRPP2 and TRPP3 proteins function as Ca2+-regulated, non-selective cation channels. During embryogenesis TRPP2 is active in node monocilia and plays a role in the establishment of left-right asymmetry. Recent results have indicated that TRPP2 interacts with polycystin-1 and that their interaction is important for their function as mechanosensitive channels at the primary cilium of renal epithelial cells. The interaction of polycystin family members appears to be conserved and is critical for fertilization and mating behavior. An emerging concept from the studies of the polycystin family is that they function as cation-influx based devices for sensing extracellular signals on ciliated structures. Here we review the function of TRPML1 and TRPP2 as representative members of these families, focusing on the genetics, physiology, and biochemistry.

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Abbreviations

TRPML:

Mucolipin gene family

TRPP:

Polycystin 2 gene family

TM:

Transmembrane segment

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Acknowledgments

We thank Erica Allen, Gregory Germino, Kuni Iwasa, and John Northup for their comments on the manuscript. R01 DK062199 and Scientist Development grant of American Heart Association (FQ) and intramural program of the National Institute on Deafness and Other Communication Disorders (KNT).

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  1. Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Feng Qian

  2. Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, 20855, USA

    Konrad Noben-Trauth

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Correspondence to Feng Qian or Konrad Noben-Trauth.

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Qian, F., Noben-Trauth, K. Cellular and molecular function of mucolipins (TRPML) and polycystin 2 (TRPP2). Pflugers Arch - Eur J Physiol 451, 277–285 (2005). https://doi.org/10.1007/s00424-005-1469-4

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