Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.
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Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6. / Poët, Mallorie; Kornak, Uwe; Schweizer, Michaela; Zdebik, Anselm A; Scheel, Olaf; Hoelter, Sabine; Wurst, Wolfgang; Schmitt, Anja; Fuhrmann, Jens C; Planells-Cases, Rosa; Mole, Sara E; Hübner, Christian; Jentsch, Thomas J.
in: P NATL ACAD SCI USA, Jahrgang 103, Nr. 37, 37, 2006, S. 13854-13859.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.
AU - Poët, Mallorie
AU - Kornak, Uwe
AU - Schweizer, Michaela
AU - Zdebik, Anselm A
AU - Scheel, Olaf
AU - Hoelter, Sabine
AU - Wurst, Wolfgang
AU - Schmitt, Anja
AU - Fuhrmann, Jens C
AU - Planells-Cases, Rosa
AU - Mole, Sara E
AU - Hübner, Christian
AU - Jentsch, Thomas J
PY - 2006
Y1 - 2006
N2 - Mammalian CLC proteins function as Cl(-) channels or as electrogenic Cl(-)/H(+) exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression in dorsal root ganglia. ClC-6 colocalized with markers for late endosomes in neuronal cell bodies. The disruption of ClC-6 in mice reduced their pain sensitivity and caused moderate behavioral abnormalities. Neuronal tissues showed autofluorescence at initial axon segments. At these sites, electron microscopy revealed electron-dense storage material that caused a pathological enlargement of proximal axons. These deposits were positive for several lysosomal proteins and other marker proteins typical for neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. However, the lysosomal pH of Clcn6(-/-) neurons appeared normal. CLCN6 is a candidate gene for mild forms of human NCL. Analysis of 75 NCL patients identified ClC-6 amino acid exchanges in two patients but failed to prove a causative role of CLCN6 in that disease.
AB - Mammalian CLC proteins function as Cl(-) channels or as electrogenic Cl(-)/H(+) exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression in dorsal root ganglia. ClC-6 colocalized with markers for late endosomes in neuronal cell bodies. The disruption of ClC-6 in mice reduced their pain sensitivity and caused moderate behavioral abnormalities. Neuronal tissues showed autofluorescence at initial axon segments. At these sites, electron microscopy revealed electron-dense storage material that caused a pathological enlargement of proximal axons. These deposits were positive for several lysosomal proteins and other marker proteins typical for neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. However, the lysosomal pH of Clcn6(-/-) neurons appeared normal. CLCN6 is a candidate gene for mild forms of human NCL. Analysis of 75 NCL patients identified ClC-6 amino acid exchanges in two patients but failed to prove a causative role of CLCN6 in that disease.
M3 - SCORING: Zeitschriftenaufsatz
VL - 103
SP - 13854
EP - 13859
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 37
M1 - 37
ER -
