Chemical Proteomics Reveals Protein Tyrosination Extends Beyond the Alpha-Tubulins in Human Cells
2022-10-11
Dmytro Makarov, Dr. Pavel Kielkowski
ChemBioChem, 23, e202200414 (1 of 6), 2022
Tubulin detyrosination-tyrosination cycle regulates the stability of microtubules. With respect to α-tubulins, the tyrosination level is maintained by a single tubulin-tyrosine ligase (TTL). However, the precise dynamics and tubulin isoforms which undergo (de)tyrosination in neurons are unknown. Here, we exploit the substrate promiscuity of the TTL to introduce an O-propargyl-l-tyrosine to neuroblastoma cells and neurons. Mass spectrometry-based chemical proteomics in neuroblastoma cells using the O-propargyl-l-tyrosine probe revealed previously discussed tyrosination of TUBA4A, MAPRE1, and other non-tubulin proteins. This finding was further corroborated in differentiating neurons. Together we present the method for tubulin tyrosination profiling in living cells. Our results show that detyrosination-tyrosination is not restricted to α-tubulins with coded C-terminal tyrosine and is thus involved in fine-tuning of the tubulin and non-tubulin proteins during neuronal differentiation.
Speaker: Prof. Dr. Thomas Carell
Ludwig-Maximilians-Universität München
Institut für Chemische Epigenetik (ICEM)
Department of Chemistry
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Managing Director: Dr. Oliver Baron
Institute for Chemical Epigenetics Munich (ICEM)
Ludwig-Maximilians-Universität München
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Institute for Chemical Epigenetics Munich (ICEM)
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LMU Munich
Department of Chemistry
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LMU Munich
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LMU Munich
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