The cell motility regulator NAA80 is assisted by Profilin 2
Actin is modified by N-terminal acetylation which regulates its role in steering cellular architecture and cell motility. Now the machinery performing this acetylation is uncovered.
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In human cells, actin is a major聽component of the cytoskeleton.聽Only recently, the聽聽and聽NAA80 mediated N-terminal acetylation of actin was revealed聽to have a strong聽impact on聽cytoskeleton dynamics and cell motility.聽
There is a machinery of seven N-terminal acetyltransferases (NATs)聽catalyzing N-terminal acetylation of totally 80% of the human proteome. Most NATs therefore have a large number of聽substrates and many operate on the ribosome to carry out聽. In contrast, actin has a dedicated NAT, NAA80, which acts post-translationally. Important insights on how actin is targeted by NAA80 and profilin was recently revealed by a聽trimeric structure of . Now, a minor isoform of profilin, profilin 2 (PFN2), emerges as the specific cellular partner for NAA80. Binding of PFN2 to NAA80 increases its intrinsic capacity to perform actin N-terminal acetylation and stabilizes the聽contact between NAA80 and its substrate actin. Thus, the key components defining how actin becomes N-terminally acetylated in human cells are now determined.
Biochemical and molecular biology investigations in the聽Arnesen lab聽at 幸运飞艇计划聽were carried out by current lab members Rasmus Ree, Laura Kind and Syvia Varland聽and alumni Minglu Dai and Adrian Drazic. Analytical ultracentrifugation experiments were performed by Anna Kaziales and Klaus Richter at the Technical University in Munich.聽
The Arnesen lab acknowledges support from Helse Vest, the Norwegian Cancer Society, the Research Council of Norway and the European Research Council (ERC). Rasmus Ree and Laura Kind are聽Postdoctoral and doctoral candidates, respectively, supported by the Medical Faculty at 幸运飞艇计划.
