PT  - JOURNAL ARTICLE
AU  - Seung Joon Lee
AU  - Amar N. Kar
AU  - Riki Kawaguchi
AU  - Priyanka Patel
AU  - Pabitra K. Sahoo
AU  - Byron Aguilar
AU  - Kelsey D. Lantz
AU  - Caylee R. McCain
AU  - Giovanni Coppola
AU  - Qun Lu
AU  - Jeffery L. Twiss
TI  - Selective axonal translation of prenylated Cdc42 mRNA isoform supports axon growth
AID  - 10.1101/366369
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 366369
4099  - http://biorxiv.org/content/early/2018/07/10/366369.short
4100  - http://biorxiv.org/content/early/2018/07/10/366369.full
AB  - The small Rho-family GTPase CDC42 has long been known to have a role in cell motility and axon growth. The eukaryotic Cdc42 gene is alternatively spliced yielding mRNAs with two different 3’UTRs and distinct C-termini, which have CaaX and CCaX motifs for post-translational prenylation or palmitoylation, respectively. Palmitoylated CDC42 protein has been shown to contribute to dendrite maturation, while the prenylated CDC42 protein contributes to axon specification. Here, we show that the mRNA encoding prenylated CDC42 protein preferentially localizes into axons of cultured sensory neurons. We show that prenylated CDC42 promotes axon growth in cultured sensory neurons, but palmitoylated CDC42 does not affect axon growth. The growth promotion by prenylated CDC42 requires axonal localization of its mRNA and an intact C-terminal CaaX motif for post-translational modification of the encoded protein by prenylation. Prenylated CDC42 protein localizes to the periphery of growth cones, but this subcellular localization requires axonal targeting of its mRNA. Together, these data show that alternative splicing of the Cdc42 gene product generates an axon growth-promoting, locally synthesized prenylated CDC42 protein.