Role of Ostm1 Cytosolic Complex with Kinesin 5B in Intracellular Dispersion and Trafficking
| Autor: | Subramanya N.M. Pandruvada, Jean Vacher, Monica Pata, Suzanne Benjannet, Nabil G. Seidah, Claude Lazure, Janie Beauregard |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Multiprotein complex Endosome Ubiquitin-Protein Ligases Molecular Sequence Data Kinesins Biology Cell Line 03 medical and health sciences Mice Cytosol Chlorocebus aethiops Animals Humans Amino Acid Sequence Caenorhabditis elegans Molecular Biology Zebrafish Endoplasmic reticulum Membrane Proteins Cell Biology Articles Subcellular localization Transmembrane protein Cell biology Transport protein Lymphocyte cytosolic protein 2 Protein Transport 030104 developmental biology Drosophila melanogaster HEK293 Cells COS Cells Kinesin Protein Processing Post-Translational Sequence Alignment |
| Popis: | In humans and in mice, mutations in the Ostm1 gene cause the most severe form of osteopetrosis, a major bone disease, and neuronal degeneration, both of which are associated with early death. To gain insight into Ostm1 function, we first investigated by sequence and biochemical analysis an immature 34-kDa type I transmembrane Ostm1 protein with a unique cytosolic tail. Mature Ostm1 is posttranslationally processed and highly N-glycosylated and has an apparent mass of ∼60 kDa. Analysis the subcellular localization of Ostm1 showed that it is within the endoplasmic reticulum, trans-Golgi network, and endosomes/lysosomes. By a wide protein screen under physiologic conditions, several novel cytosolic Ostm1 partners were identified and validated, for which a direct interaction with the kinesin 5B heavy chains was demonstrated. These results determined that Ostm1 is part of a cytosolic scaffolding multiprotein complex, imparting an adaptor function to Ostm1. Moreover, we uncovered a role for the Ostm1/KIF5B complex in intracellular trafficking and dispersion of cargos from the endoplasmic reticulum to late endosomal/lysosomal subcellular compartments. These Ostm1 molecular and cellular functions could elucidate all of the pathophysiologic mechanisms underlying the wide phenotypic spectrum of Ostm1-deficient mice. |
| Databáze: | OpenAIRE |
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