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TRPML Channels and Mucolipidosis Type IV

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Pathologies of Calcium Channels

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Abstract

The transient receptor potential (TRP) mucolipin channels TRPML1, TRPML2, and TRPML3 are non-selective cation channels predominantly found in the endolysosomal system. Mutations in the TRPML1 gene (also known as MCOLN1) cause mucolipidosis type IV in humans manifested by psychomotor abnormalities, corneal clouding, retinal degeneration, and progressive neurodegeneration. The recent identification of small compound chemical activators for TRPML channels has opened up the possibility to study TRPML mutant and wild-type isoforms both in vitro and in vivo in more detail. These compounds will permit further investigation on the functional roles of TRPML channels in the endolysosomal system. Ultimately, these drugs or their derivatives could be used to design selective pharmacological tools to gate and rescue specific loss-of-function point mutations in TRPML1 that cause mucolipidosis type IV. Recently discovered TRPML channel interaction partners may serve as alternative pharmacological targets for the treatment of mucolipidosis type IV.

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Authors and Affiliations

  1. Department of Pharmacy—Center for Drug Research and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität, Munich, Germany

    Christian Grimm

  2. Department of Biological Science and Center for Applied Biotechnology Studies, California State University, Fullerton, CA, USA

    Math P. Cuajungco

  3. Mental Health Research Institute, Melbourne Brain Centre, Parkville, VIC, Australia

    Math P. Cuajungco

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  1. Christian Grimm
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  2. Math P. Cuajungco
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Correspondence to Christian Grimm .

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  1. Hotchkiss Brain Institute, Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada

    Norbert Weiss

  2. Department of Neurophysiology and Pharmacology, Medical University Vienna, Vienna, Austria

    Alexandra Koschak

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Grimm, C., Cuajungco, M.P. (2014). TRPML Channels and Mucolipidosis Type IV . In: Weiss, N., Koschak, A. (eds) Pathologies of Calcium Channels. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40282-1_19

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