2. Academic Validation
  3. Posttranslational modification of microtubules by the MATCAP detyrosinase

Posttranslational modification of microtubules by the MATCAP detyrosinase

  • Science. 2022 May 20;376(6595):eabn6020. doi: 10.1126/science.abn6020.
Lisa Landskron 1,  Jitske Bak 1,  Athanassios Adamopoulos 1,  Konstantina Kaplani 2,  Maria Moraiti 1,  Lisa G van den Hengel 1,  Ji-Ying Song 3,  Onno B Bleijerveld 4,  Joppe Nieuwenhuis 5,  Tatjana Heidebrecht 1,  Linda Henneman 6,  Marie-Jo Moutin 7,  Marin Barisic 8 9,  Stavros Taraviras 2,  Anastassis Perrakis 1,  Thijn R Brummelkamp 1
Affiliations

Affiliations

  • 1 Oncode Institute, Division of Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands.
  • 2 Department of Physiology, School of Medicine, University of Patras, 26504 Patras, Greece.
  • 3 Experimental Animal Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands.
  • 4 Proteomics Facility, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands.
  • 5 Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, Netherlands.
  • 6 Transgenic Core Facility, Mouse Clinic for Cancer and Aging (MCCA), Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands.
  • 7 Université Grenoble Alpes, INSERM, U1216, CNRS, Grenoble Institut Neurosciences, 38000 Grenoble, France.
  • 8 Cell Division and Cytoskeleton, Danish Cancer Society Research Center (DCRC), 2100 Copenhagen, Denmark.
  • 9 Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
PMID: 35482892 DOI: 10.1126/science.abn6020
Abstract

The detyrosination-tyrosination cycle involves the removal and religation of the C-terminal tyrosine of α-tubulin and is implicated in cognitive, cardiac, and mitotic defects. The vasohibin-small vasohibin-binding protein (SVBP) complex underlies much, but not all, detyrosination. We used haploid genetic screens to identify an unannotated protein, microtubule associated tyrosine Carboxypeptidase (MATCAP), as a remaining detyrosinating Enzyme. X-ray crystallography and cryo-electron microscopy structures established MATCAP's cleaving mechanism, substrate specificity, and microtubule recognition. Paradoxically, whereas abrogation of tyrosine religation is lethal in mice, codeletion of MATCAP and SVBP is not. Although viable, defective detyrosination caused microcephaly, associated with proliferative defects during neurogenesis, and abnormal behavior. Thus, MATCAP is a missing component of the detyrosination-tyrosination cycle, revealing the importance of this modification in brain formation.

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