RGD Reference Report - The Golgi Outpost Protein TPPP Nucleates Microtubules and Is Critical for Myelination. - Rat Genome Database

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

Authors: Fu, Meng-Meng  McAlear, Thomas S  Nguyen, Huy  Oses-Prieto, Juan A  Valenzuela, Alex  Shi, Rebecca D  Perrino, John J  Huang, Ting-Ting  Burlingame, Alma L  Bechstedt, Susanne  Barres, Ben A 
Citation: Fu MM, etal., Cell. 2019 Sep 19;179(1):132-146.e14. doi: 10.1016/j.cell.2019.08.025. Epub 2019 Sep 12.
RGD ID: 14995310
Pubmed: PMID:31522887   (View Abstract at PubMed)
PMCID: PMC7214773   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2019.08.025   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TpppRatpostsynaptic Golgi apparatus located_inIDA PMID:31522887UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Tppp  (tubulin polymerization promoting protein)


Additional Information