13
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Accumulation of Laminin Monomers in Drosophila Glia Leads to Glial Endoplasmic Reticulum Stress and Disrupted Larval Locomotion

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The nervous system is surrounded by an extracellular matrix composed of large glycoproteins, including perlecan, collagens, and laminins. Glial cells in many organisms secrete laminin, a large heterotrimeric protein consisting of an α, β, and γ subunit. Prior studies have found that loss of laminin subunits from vertebrate Schwann cells causes loss of myelination and neuropathies, results attributed to loss of laminin-receptor signaling. We demonstrate that loss of the laminin γ subunit (LanB2) in the peripheral glia of Drosophila melanogaster results in the disruption of glial morphology due to disruption of laminin secretion. Specifically, knockdown of LanB2 in peripheral glia results in accumulation of the β subunit (LanB1), leading to distended endoplasmic reticulum (ER), ER stress, and glial swelling. The physiological consequences of disruption of laminin secretion in glia included decreased larval locomotion and ultimately lethality. Loss of the γ subunit from wrapping glia resulted in a disruption in the glial ensheathment of axons but surprisingly did not affect animal locomotion. We found that Tango1, a protein thought to exclusively mediate collagen secretion, is also important for laminin secretion in glia via a collagen-independent mechanism. However loss of secretion of the laminin trimer does not disrupt animal locomotion. Rather, it is the loss of one subunit that leads to deleterious consequences through the accumulation of the remaining subunits.

          SIGNIFICANCE STATEMENT This research presents a new perspective on how mutations in the extracellular matrix protein laminin cause severe consequences in glial wrapping and function. Glial-specific loss of the β or γ laminin subunit disrupted glia morphology and led to ER expansion and stress due to retention of other subunits. The retention of the unpaired laminin subunit was key to the glial disruption as loss of Tango1 blocked secretion of the complete laminin trimer but did not lead to glial or locomotion defects. The effects were observed in the perineurial glia that envelope the peripheral and central nervous systems, providing evidence for the importance of this class of glia in supporting nervous system function.

          Related collections

          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          27 January 2016
          : 36
          : 4
          : 1151-1164
          Affiliations
          [1] 1Departments of Zoology and
          [2] 2Psychology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada, and
          [3] 3Neuroscience Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
          Author notes
          Correspondence should be addressed to Vanessa J. Auld, 2350 Health Sciences Mall, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. auld@ 123456zoology.ubc.ca

          Author contributions: L.M.P.-R. and V.J.A. designed research; L.M.P.-R. performed research; E.L.A. and C.H.R. contributed unpublished reagents/analytic tools; L.M.P.-R. and V.J.A. analyzed data; L.M.P.-R. and V.J.A. wrote the paper.

          Author information
          http://orcid.org/0000-0002-1781-0654
          http://orcid.org/0000-0003-3976-9186
          Article
          PMC6604820 PMC6604820 6604820 1797-15
          10.1523/JNEUROSCI.1797-15.2016
          6604820
          26818504
          3f50fe4d-b494-4047-ac6d-51f07a448265
          Copyright © 2016 the authors 0270-6474/16/361151-14$15.00/0
          History
          : 3 May 2015
          : 30 October 2015
          : 9 December 2015
          Categories
          Articles
          Cellular/Molecular
          Custom metadata
          true

          Drosophila ,ER stress,Tango1,glia,laminin,neuropathy
          Drosophila , ER stress, Tango1, glia, laminin, neuropathy

          Comments

          Comment on this article