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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Auer-Grumbach, M; Olschewski, A; Papić, L; Kremer, H; McEntagart, ME; Uhrig, S; Fischer, C; Fröhlich, E; Bálint, Z; Tang, B; Strohmaier, H; Lochmüller, H; Schlotter-Weigel, B; Senderek, J; Krebs, A; Dick, KJ; Petty, R; Longman, C; Anderson, NE; Padberg, GW; Schelhaas, HJ; van Ravenswaaij-Arts, CM; Pieber, TR; Crosby, AH; Guelly, C.
Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
Nat Genet. 2010; 42(2):160-164 Doi: 10.1038/ng.508 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Auer-Grumbach Michaela
Co-Autor*innen der Med Uni Graz
Balint Zoltan
Fischer Carina
Fröhlich Eleonore
Gülly Christian
Krebs Angelika
Olschewski Andrea
Papic Lea
Pieber Thomas
Strohmaier Heimo
Tang Bi
Uhrig Sabine

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Spinal muscular atrophies (SMA, also known as hereditary motor neuropathies) and hereditary motor and sensory neuropathies (HMSN) are clinically and genetically heterogeneous disorders of the peripheral nervous system. Here we report that mutations in the TRPV4 gene cause congenital distal SMA, scapuloperoneal SMA, HMSN 2C. We identified three missense substitutions (R269H, R315W and R316C) affecting the intracellular N-terminal ankyrin domain of the TRPV4 ion channel in five families. Expression of mutant TRPV4 constructs in cells from the HeLa line revealed diminished surface localization of mutant proteins. In addition, TRPV4-regulated Ca(2+) influx was substantially reduced even after stimulation with 4alphaPDD, a TRPV4 channel-specific agonist, and with hypo-osmotic solution. In summary, we describe a new hereditary channelopathy caused by mutations in TRPV4 and present evidence that the resulting substitutions in the N-terminal ankyrin domain affect channel maturation, leading to reduced surface expression of functional TRPV4 channels.
Find related publications in this database (using NLM MeSH Indexing)
Amino Acid Substitution - genetics
Ankyrin Repeat -
Calcium - metabolism
HeLa Cells -
Hereditary Sensory and Motor Neuropathy - complications
Hereditary Sensory and Motor Neuropathy - genetics
Hereditary Sensory and Motor Neuropathy - physiopathology
Humans -
Immunohistochemistry -
Intracellular Space - metabolism
Ion Channel Gating -
Models, Molecular -
Molecular Sequence Data -
Muscular Atrophy, Spinal - complications
Muscular Atrophy, Spinal - congenital
Muscular Atrophy, Spinal - genetics
Muscular Atrophy, Spinal - physiopathology
Mutant Proteins - metabolism
Mutation - genetics
Osmosis -
TRPV Cation Channels - chemistry
TRPV Cation Channels - genetics
Transfection -

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