Axonal Signaling Proteins Take the ER Highway.docVIP

Synopsis AxonalSignalingProteinsTaketheERHighway RichardRobinson* FreelanceScienceWriter,Sherborn,Massachusetts,UnitedStatesofAmerica It’s a long way from the cell body ofa neuron to its axonal tip—several feet or moreinthelongesthumanneurons,and, eveninthesmallestones,thelengthofthe axon can be hundreds of times the width ofthecell.Transportingcargoalongthat distance is primarily the job of microtu- bulesofthecytoskeleton,butitisaidedin some small measure by the endoplasmic reticulum (ER), a system of internal membranes that is continuous with the nuclear membrane and pervades the cell. But theERhas notbeenthought toplay much of a role in transport of proteins over such long distances. That view has begun to change recently, however, as a smallnumberofproteinshavebeenshown to be trafficked within the ER along the length of the axon. In this issue of PLoS Biology, Shaul Yogev, Eyal Schejter, and Ben-Zion Shilo add to that list and show thatitincludesaclusterofproteinswhose combined action plays a key role in developmentoftheflyvisualsystem. In the developing visual system of Drosophila, the axons of photoreceptor neurons grow until they reach a target layer on the outer surface of the brain called the lamina. There, they release a seriesofproteinsthattriggerneurogenesis in lamina precursor cells. One of these factorsisaligandfortheepidermalgrowth factor receptor. The ligand, called Spitz, requiresaninternalchaperonecalledStar to get it where it is going and must be cleaved by a protease called Rhomboid-3 beforeitisreleasedinitsactiveform.The authorsbegantheirinvestigationbyshow- ing that there was no Rho-3 messenger RNA in the axon, suggesting that, unlike manyotherproteinsattheaxonterminus, Rho-3 is not synthesized from mRNA transported along microtubules to the axontip. Localization of the Drosophila EGF receptor ligand and its processing machinery within the endoplasmic reticulum of photoreceptor cells is essential for axonal traffickingandsecretionofthel