Posttranslational modification of microtubules by the MATCAP detyrosinase

Lisa Landskron; Jitske Bak; Athanassios Adamopoulos; Konstantina Kaplani; Maria Moraiti; Lisa G. van den Hengel; Ji Ying Song; Onno B. Bleijerveld; Joppe Nieuwenhuis; Tatjana Heidebrecht; Linda Henneman; Marie Jo Moutin; Marin Barisic; Stavros Taraviras; Anastassis Perrakis; Thijn R. Brummelkamp

doi:10.1126/science.abn6020

Posttranslational modification of microtubules by the MATCAP detyrosinase

Lisa Landskron, Jitske Bak, Athanassios Adamopoulos, Konstantina Kaplani, Maria Moraiti, Lisa G. van den Hengel, Ji Ying Song, Onno B. Bleijerveld, Joppe Nieuwenhuis, Tatjana Heidebrecht, Linda Henneman, Marie Jo Moutin, Marin Barisic, Stavros Taraviras, Anastassis Perrakis^*, Thijn R. Brummelkamp

^*Corresponding author for this work

Morphogenesis and Differentiation Program

Research output: Contribution to journal › Journal article › Research › peer-review

31 Citations (Scopus)

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Abstract

The detyrosination-tyrosination cycle involves the removal and religation of the C-terminal tyrosine of a-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.

Original language	English
Article number	eabn6020
Journal	Science
Volume	376
Issue number	6595
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.abn6020
Publication status	Published - 2022

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© 2022 American Association for the Advancement of Science. All rights reserved.

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Landskron, L., Bak, J., Adamopoulos, A., Kaplani, K., Moraiti, M., van den Hengel, L. G., Song, J. Y., Bleijerveld, O. B., Nieuwenhuis, J., Heidebrecht, T., Henneman, L., Moutin, M. J., Barisic, M., Taraviras, S., Perrakis, A., & Brummelkamp, T. R. (2022). Posttranslational modification of microtubules by the MATCAP detyrosinase. Science, 376(6595), [eabn6020]. https://doi.org/10.1126/science.abn6020

Posttranslational modification of microtubules by the MATCAP detyrosinase. / Landskron, Lisa; Bak, Jitske; Adamopoulos, Athanassios; Kaplani, Konstantina; Moraiti, Maria; van den Hengel, Lisa G.; Song, Ji Ying; Bleijerveld, Onno B.; Nieuwenhuis, Joppe; Heidebrecht, Tatjana; Henneman, Linda; Moutin, Marie Jo; Barisic, Marin; Taraviras, Stavros; Perrakis, Anastassis; Brummelkamp, Thijn R.

In: Science, Vol. 376, No. 6595, eabn6020, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Landskron, L, Bak, J, Adamopoulos, A, Kaplani, K, Moraiti, M, van den Hengel, LG, Song, JY, Bleijerveld, OB, Nieuwenhuis, J, Heidebrecht, T, Henneman, L, Moutin, MJ, Barisic, M, Taraviras, S, Perrakis, A & Brummelkamp, TR 2022, 'Posttranslational modification of microtubules by the MATCAP detyrosinase', Science, vol. 376, no. 6595, eabn6020. https://doi.org/10.1126/science.abn6020

Landskron, Lisa ; Bak, Jitske ; Adamopoulos, Athanassios ; Kaplani, Konstantina ; Moraiti, Maria ; van den Hengel, Lisa G. ; Song, Ji Ying ; Bleijerveld, Onno B. ; Nieuwenhuis, Joppe ; Heidebrecht, Tatjana ; Henneman, Linda ; Moutin, Marie Jo ; Barisic, Marin ; Taraviras, Stavros ; Perrakis, Anastassis ; Brummelkamp, Thijn R. / Posttranslational modification of microtubules by the MATCAP detyrosinase. In: Science. 2022 ; Vol. 376, No. 6595.

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title = "Posttranslational modification of microtubules by the MATCAP detyrosinase",

abstract = "The detyrosination-tyrosination cycle involves the removal and religation of the C-terminal tyrosine of a-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{\textquoteright}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.",

author = "Lisa Landskron and Jitske Bak and Athanassios Adamopoulos and Konstantina Kaplani and Maria Moraiti and {van den Hengel}, {Lisa G.} and Song, {Ji Ying} and Bleijerveld, {Onno B.} and Joppe Nieuwenhuis and Tatjana Heidebrecht and Linda Henneman and Moutin, {Marie Jo} and Marin Barisic and Stavros Taraviras and Anastassis Perrakis and Brummelkamp, {Thijn R.}",

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AU - Landskron, Lisa

AU - Bak, Jitske

AU - Adamopoulos, Athanassios

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AU - Moraiti, Maria

AU - van den Hengel, Lisa G.

AU - Song, Ji Ying

AU - Bleijerveld, Onno B.

AU - Nieuwenhuis, Joppe

AU - Heidebrecht, Tatjana

AU - Henneman, Linda

AU - Moutin, Marie Jo

AU - Barisic, Marin

AU - Taraviras, Stavros

AU - Perrakis, Anastassis

AU - Brummelkamp, Thijn R.

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N2 - The detyrosination-tyrosination cycle involves the removal and religation of the C-terminal tyrosine of a-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.

AB - The detyrosination-tyrosination cycle involves the removal and religation of the C-terminal tyrosine of a-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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