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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell Dev. Biol. | doi: 10.3389/fcell.2019.00176

Misplaced Golgi Elements Produce Randomly Oriented Microtubules and Aberrant Cortical Arrays of Microtubules in Dystrophic Skeletal Muscle Fibers

Sarah Oddoux1, 2,  Davide Randazzo1, 2,  Aster Kenea1, 2, Bruno Alonso1, 2, Kristien J. Zaal1, 2 and  Evelyn Ralston1, 2*
  • 1Light Imaging Section (NIAMS), United States
  • 2National Institutes of Health (NIH), United States

Golgi complex and microtubules reorganize entirely during muscle differentation and maturation. The final organization is completely different from that in proliferating cells. Thousands of Golgi elements (GE), small stacks of cisternae, are positioned along nuclear membranes and along microtubules throughout the large multinucleated muscle fibers. GE serve as microtubule-organizing centers as do nuclear membranes. Disorganization of the Golgi-microtubule network in muscle diseases and in experimental conditions have pointed to factors that contribute to its regulation in muscle. Among these are the protein dystrophin that is missing in Duchenne muscular dystrophy and in the mdx mouse model of Duchenne muscular dystrophy, muscle's patterned activity, and the -tubulin tubb6 that is increased in Duchenne muscular dystrophy, mdx, and in an experimental muscle regeneration model. To investigate GE-microtubule network differences between wild-type and mdx muscles we have now followed GFP-tagged microtubule markers in live mdx muscle fibers and have studied recovery of their GE- microtubule network from microtubule depolymerization by nocodazole. Compared to wild-type microtubules, mdx microtubules grow modestly but significantly faster. They also show a considerably larger proportion of microtubules dissociated from GE. This does not result from a lack of GE. In both mdx and tubb6 overexpressing muscle fibers, GE are increased in number and size. The muscle-characteristic association of GE with ER exit sites is maintained in mdx and tubb6 overexpressing muscle fibers whose ER exit sites are also increased in number and size. Finally, counting the association of the cis-Golgi marker GM130 in immunostained fibers with markers of ER exit sites (Sec31), cis- and trans-Golgi (GM130 and GLUT4) and of the ER-Golgi intermediate compartment (p58) reveal that each muscle GE is a full, small, Golgi complex.

Keywords: Muscle, mdx, Golgi, microtubule, ERes, ERGIC, MTOC, tubb6

Received: 13 May 2019; Accepted: 13 Aug 2019.

Edited by:

Jaakko Saraste, University of Bergen, Norway

Reviewed by:

Martin Lowe, University of Manchester, United Kingdom
Antonino Colanzi, Institute of Biochemistry and Cell Biology (CNR), Italy  

Copyright: © 2019 Oddoux, Randazzo, Kenea, Alonso, Zaal and Ralston. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Evelyn Ralston, National Institutes of Health (NIH), Bethesda, 9000, Maryland, United States, ralstone@mail.nih.gov