title: Global and local mechanisms sustain axonal proteostasis of transmembrane proteins.
abstract: The control of neuronal protein homeostasis orproteostasisis tightly regulated both spatially and temporally, assuring accurate and integrated responses to external or intrinsic stimuli. Local or autonomous responses in dendritic and axonal compartments are crucial to sustain function during development, physiology and in response to damage or disease. Axons are responsible for generating and propagating electrical impulses in neurons, and the establishment and maintenance of their molecular composition are subject to extreme constraints exerted by length and size. Proteins that require the secretory pathway, such as receptors, transporters, ion channels or cell adhesion molecules, are fundamental for axonal function, but whether axons regulate their abundance autonomously and how they achieve this is not clear. Evidence supports the role of three complementary mechanisms to maintain proteostasis of these axonal proteins, namely vesicular transport, local translation and trafficking and transfer from supporting cells. Here, we review these mechanisms, their molecular machineries and contribution to neuronal function. We also examine the signaling pathways involved in local translation and their role during development and nerve injury. We discuss the relative contributions of a transport-controlled proteome directed by the soma (global regulation) versus a local-controlled proteome based on local translation or cell transfer (local regulation).
authors.affiliation: Program of Physiology and Biophysics, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile.|Biomedical Neuroscience Institute, Universidad de Chile, Santiago, Chile.
authors.forename: Víctor Hugo
authors.initials: VH
authors.lastname: Cornejo
authors.affiliation: Program of Physiology and Biophysics, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile.|Biomedical Neuroscience Institute, Universidad de Chile, Santiago, Chile.
authors.forename: Alejandro
authors.identifier: 0000-0001-9138-1854
authors.initials: A
authors.lastname: Luarte
authors.affiliation: Program of Physiology and Biophysics, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile.|Biomedical Neuroscience Institute, Universidad de Chile, Santiago, Chile.
authors.forename: Andrés
authors.initials: A
authors.lastname: Couve
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D008565:Membrane Proteins
keywords: axon; neurons; protein synthesis; proteome; proteostasis; trafficking; transmembrane proteins; transport