2. Academic Validation
  3. The Golgi Outpost Protein TPPP Nucleates Microtubules and Is Critical for Myelination

The Golgi Outpost Protein TPPP Nucleates Microtubules and Is Critical for Myelination

  • Cell. 2019 Sep 19;179(1):132-146.e14. doi: 10.1016/j.cell.2019.08.025.
Meng-Meng Fu 1,  Thomas S McAlear 2,  Huy Nguyen 3,  Juan A Oses-Prieto 4,  Alex Valenzuela 5,  Rebecca D Shi 6,  John J Perrino 7,  Ting-Ting Huang 8,  Alma L Burlingame 4,  Susanne Bechstedt 9,  Ben A Barres 5
Affiliations

Affiliations

  • 1 Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: mengmengfu@gmail.com.
  • 2 Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada.
  • 3 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 4 Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 5 Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 6 Neuroscience Graduate Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 7 Cell Science Imaging Facility, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 8 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Geriatric Research, Education, and Care Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • 9 Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada. Electronic address: susanne.bechstedt@mcgill.ca.
PMID: 31522887 DOI: 10.1016/j.cell.2019.08.025
Abstract

Oligodendrocytes extend elaborate microtubule arbors that contact up to 50 axon segments per cell, then spiral around myelin sheaths, penetrating from outer to inner layers. However, how they establish this complex cytoarchitecture is unclear. Here, we show that oligodendrocytes contain Golgi outposts, an organelle that can function as an acentrosomal microtubule-organizing center (MTOC). We identify a specific marker for Golgi outposts-TPPP (tubulin polymerization promoting protein)-that we use to purify this organelle and characterize its proteome. In in vitro cell-free assays, recombinant TPPP nucleates microtubules. Primary oligodendrocytes from Tppp knockout (KO) mice have aberrant microtubule branching, mixed microtubule polarity, and shorter myelin sheaths when cultured on 3-dimensional (3D) microfibers. Tppp KO mice exhibit hypomyelination with shorter, thinner myelin sheaths and motor coordination deficits. Together, our data demonstrate that microtubule nucleation outside the cell body at Golgi outposts by TPPP is critical for elongation of the myelin sheath.

Keywords

Golgi outpost; TPPP; branching; mass spectrometry; microtubule; myelin; nucleation; oligodendrocyte.

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