title: Translation of the cell adhesion molecule ALCAM in axonal growth cones - regulation and functional importance.
abstract: ALCAM is a cell adhesion molecule that is present on extending axons and has been shown to be crucial for elongation and navigation of retinal ganglion cell (RGC) axons. In the present study, we show that ALCAM mRNA is present in axonal growth cones of RGCs in vivo and in vitro, and that translation of ALCAM occurs in RGC growth cones separated from their soma. This growth cone translation is regulated by the 3'-untranslated region (3'-UTR) of ALCAM and depends on the activity of the kinases ERK and TOR (target of rapamycin). We also investigated the impact of the growth cone translation of ALCAM on axonal functions. Growth cone translation of ALCAM is crucial for the enhanced elongation of axons extending in contact with ALCAM protein. The local translation of ALCAM in the growth cone is able to rapidly counterbalance experimentally induced ALCAM internalization, thereby contributing to the maintenance of constant ALCAM levels in the plasma membrane. Assays where RGC axons have the choice to grow on laminin or both ALCAM and laminin - as is the case in the developing retina - reveal that the axonal preference for ALCAM-containing lanes depends on translation of ALCAM in growth cones. Taken together, these results show for the first time that translation of a cell adhesion molecule in growth cones, as well as the impact of this local translation on the behavior of axon and growth cone.
authors.affiliation: Department of Developmental Neurobiology, Centre for Organismal Studies, University of Heidelberg, 69120 Heidelberg, Im Neuenheimer Feld 232,  Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Thelen
authors.forename: Bettina
authors.initials: B
authors.lastname: Maier
authors.forename: Marc
authors.initials: M
authors.lastname: Faber
authors.forename: Christian
authors.initials: C
authors.lastname: Albrecht
authors.forename: Paulina
authors.initials: P
authors.lastname: Fischer
authors.forename: G Elisabeth
authors.initials: GE
authors.lastname: Pollerberg
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002642:Chick Embryo; D004705:Endocytosis; D005786:Gene Expression Regulation; D020439:Growth Cones / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology
chemical_list: D020413:3' Untranslated Regions; D020410:Activated-Leukocyte Cell Adhesion Molecule; D012333:RNA, Messenger