Cell Rep. 2016 Aug 9;16(6):1664-76. doi: 10.1016/j.celrep.2016.07.005. Epub 2016 Jul 28.
Perry, RB; Rishal, I; Doron-Mandel, E; Kalinski, AL; Medzihradszky, KF; Terenzio, M; Alber, S; Koley, S; Lin, A; Rozenbaum, M; Yudin, D; Sahoo, PK; Gomes, C; Shinder, V; Geraisy, W; Huebner, EA; Woolf, CJ; Yaron, A; Burlingame, AL; Twiss, JL; Fainzilber, M
Weizmann Institute of Science, Rehovot 76100, Israel. University of South Carolina, Columbia, SC 29208; University of California, San Francisco, CA 94158; Boston Children's Hospital and Harvard Medical School, MA 02115, USA.
How can cells sense their own size to coordinate biosynthesis and metabolism with their growth needs? We recently proposed a motor-dependent bidirectional transport mechanism for axon length and cell size sensing, but the nature of the motor-transported size signals remained elusive. Here, we show that motor-dependent mRNA localization regulates neuronal growth and cycling cell size. We found that the RNA-binding protein nucleolin is associated with importin β1 mRNA in axons. Perturbation of nucleolin association with kinesins reduces its levels in axons, with a concomitant reduction in axonal importin β1 mRNA and protein levels. Strikingly, subcellular sequestration of nucleolin or importin β1 enhances axonal growth and causes a subcellular shift in protein synthesis. Similar findings were obtained in fibroblasts. Thus, subcellular mRNA localization regulates size and growth in both neurons and cycling cells.
The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 350 scientific publications are based on research using Ozgene mice.