Demetriadou, Anthi The Cyprus Institute of Neurology and Genetics|The Cyprus School of Molecular Medicine
Morales-Sanfrutos, Julia Imperial College London
Nearchou, Marianna The Cyprus Institute of Neurology and Genetics
Baba, Otto Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kyriacou, Kyriacos The Cyprus School of Molecular Medicine|The Cyprus Institute of Neurology and Genetics
Tate, Edward W. Imperial College London
Drousiotou, Anthi The Cyprus Institute of Neurology and Genetics|The Cyprus School of Molecular Medicine
Petrou, Petros P. The Cyprus Institute of Neurology and Genetics|The Cyprus School of Molecular Medicine
Organized smooth endoplasmic reticulum
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 that N-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.
Journal of Cell Science
The Company of Biologists
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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