RRC ID 73535
著者 Sato K, Suzuki-Utsunomiya K, Mitsui S, Ono S, Shimakura K, Otomo A, Hadano S.
タイトル Central nervous system specific high molecular weight ALS2/alsin homophilic complex is enriched in mouse brain synaptosomes.
ジャーナル Biochem Biophys Res Commun
Abstract ALS2/alsin, the causative gene product for a number of juvenile recessive motor neuron diseases, acts as a guanine nucleotide exchange factor (GEF) for Rab5, regulating early endosome trafficking and maturation. It has been demonstrated that ALS2 forms a tetramer, and this oligomerization is essential for its GEF activity and endosomal localization in established cancer cells. However, despite that ALS2 deficiency is implicated in neurological diseases, neither the subcellular distribution of ALS2 nor the form of its complex in the central nervous system (CNS) has been investigated. In this study, we showed that ALS2 in the brain was enriched both in synaptosomal and cytosolic fractions, while those in the liver were almost exclusively present in cytosolic fraction by differential centrifugation. Gel filtration chromatography revealed that cytosolic ALS2 prepared both from the brain and liver formed a tetramer. Remarkably, synaptosomal ALS2 existed as a high-molecular weight complex in addition to a tetramer. Such complex was also observed not only in embryonic brain but also several neuronal and glial cultures, but not in fibroblast-derived cell lines. Thus, the high-molecular weight ALS2 complex represents a unique form of ALS2-homophilic oligomers in the CNS, which may play a role in the maintenance of neural function.
巻・号 638
ページ 168-175
公開日 2023-1-1
DOI 10.1016/j.bbrc.2022.11.061
PII S0006-291X(22)01610-2
PMID 36459881
MeSH Amyotrophic Lateral Sclerosis* / metabolism Animals Brain / metabolism Central Nervous System / metabolism Endosomes / metabolism Guanine Nucleotide Exchange Factors / metabolism Mice Molecular Weight Synaptosomes* / metabolism
IF 2.985
リソース情報
ヒト・動物細胞 C6(RCB2854) RCR-1(RCB1456)