title: Mouse Stbd1 isN-myristoylated and affects ER-mitochondria association and mitochondrial morphology.
abstract: Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to bulk ER, Stbd1 was found to localize to mitochondria-associated membranes (MAMs), which represent regions of close apposition between the ER and mitochondria. We demonstrate thatN-myristoylation and binding of Stbd1 to glycogen act as major determinants of its subcellular targeting. Moreover, overexpression of non-myristoylated Stbd1 enhanced the association between ER and mitochondria, and further induced prominent mitochondrial fragmentation and clustering. Conversely, shRNA-mediated Stbd1 silencing resulted in an increase in the spacing between ER and mitochondria, and an altered morphology of the mitochondrial network, suggesting elevated fusion and interconnectivity of mitochondria. Our data unravel the molecular mechanism underlying Stbd1 subcellular targeting, support and expand its proposed function as a selective autophagy receptor for glycogen and uncover a new role for the protein in the physical association between ER and mitochondria.
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, Nicosia 1683, Cyprus.|The Cyprus School of Molecular Medicine, P. O. Box 23462, Nicosia 1683, Cyprus.
authors.forename: Anthi
authors.initials: A
authors.lastname: Demetriadou
authors.affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Morales-Sanfrutos
authors.affiliation: Department of Electron Microscopy / Molecular Pathology, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, Nicosia 1683, Cyprus.
authors.forename: Marianna
authors.initials: M
authors.lastname: Nearchou
authors.affiliation: Oral and Maxillofacial Anatomy, Faculty of Dentistry, Tokushima University, Tokushima 770-8504, Japan.
authors.forename: Otto
authors.initials: O
authors.lastname: Baba
authors.affiliation: The Cyprus School of Molecular Medicine, P. O. Box 23462, Nicosia 1683, Cyprus.|Department of Electron Microscopy / Molecular Pathology, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, Nicosia 1683, Cyprus.
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Kyriacou
authors.affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, Nicosia 1683, Cyprus.|The Cyprus School of Molecular Medicine, P. O. Box 23462, Nicosia 1683, Cyprus.
authors.forename: Anthi
authors.initials: A
authors.lastname: Drousiotou
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, Nicosia 1683, Cyprus petrosp@cing.ac.cy.|The Cyprus School of Molecular Medicine, P. O. Box 23462, Nicosia 1683, Cyprus.
authors.forename: Petros P
authors.identifier: 0000-0003-3238-3854
authors.initials: PP
authors.lastname: Petrou
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D020868:Gene Silencing; D006003:Glycogen / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009124:Muscle Proteins / Q000378:metabolism*; D019814:Myristic Acid / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D006003:Glycogen; D008565:Membrane Proteins; D009124:Muscle Proteins; D019814:Myristic Acid; C116148:STBD1 protein, human; C585769:starch-binding domain-containing protein 1, mouse
keywords: Endoplasmic reticulum; Glycogen; Mitochondria; Mitochondria-associated membranes; N-myristoylation; Organized smooth endoplasmic reticulum; Stbd1