Novel interactions of CLN3 protein link Batten disease to dysregulation of fodrin-Na, K ATPase complex

Kristiina Uusi-Rauva, Kaisu Luiro, Kimmo Tanhuanpää, Outi Kopra, Pablo Martin-Vasallo, Aija Kyttälä, Anu Jalanko

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease) is the most common progressive neurodegenerative disorder of childhood. CLN3, the transmembrane protein underlying JNCL, is proposed to participate in multiple cellular events including membrane trafficking and cytoskeletal functions. We demonstrate here that CLN3 interacts with the plasma membrane-associated cytoskeletal and endocytic fodrin and the associated Na+, K+ ATPase. The ion pumping activity of Na+, K+ ATPase was unchanged in Cln3(-/-) mouse primary neurons. However, the immunostaining pattern of fodrin appeared abnormal in JNCL fibroblasts and Cln3(-/-) mouse brains suggesting disturbances in the fodrin cytoskeleton. Furthermore, the basal subcellular distribution as well as ouabain-induced endocytosis of neuron-specific Na+, K+ ATPase were remarkably affected in Cln3(-/-) mouse primary neurons. These data suggest that CLN3 is involved if the regulation of plasma membrane fodrin cytoskeleton and consequently, the plasma membrane association of Na+, K+ ATPase. Most of the processes regulated by multi functional fodrin and Na+, K+ ATPase are also affected in JNCL and Cln3-deficiency implicating that dysregulation of fodrin cytoskeleton and non-pumping functions of Na+, K+ ATPase may play a role in the neuronal degeneration in JNCL. (c) 2008 Published by Elsevier Inc.
Alkuperäiskielienglanti
LehtiExperimental Cell Research
Vuosikerta314
Numero15
Sivut2895-2905
Sivumäärä11
ISSN0014-4827
DOI - pysyväislinkit
TilaJulkaistu - 2008
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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