title: SAD kinases control the maturation of nerve terminals in the mammalian peripheral and central nervous systems.
abstract: Axons develop in a series of steps, beginning with specification, outgrowth, and arborization, and terminating with formation and maturation of presynaptic specializations. We found previously that the SAD-A and SAD-B kinases are required for axon specification and arborization in subsets of mouse neurons. Here, we show that following these steps, SAD kinases become localized to synaptic sites and are required within presynaptic cells for structural and functional maturation of synapses in both peripheral and central nervous systems. Deleting SADs from sensory neurons can perturb either axonal arborization or nerve terminal maturation, depending on the stage of deletion. Thus, a single pair of kinases plays multiple, sequential roles in axonal differentiation.
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138.
authors.forename: Brendan N
authors.initials: BN
authors.lastname: Lilley
authors.forename: Arjun
authors.initials: A
authors.lastname: Krishnaswamy
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Masashi
authors.initials: M
authors.lastname: Kishi
authors.forename: Eric
authors.initials: E
authors.lastname: Frank
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
mesh_terms: D000483:Alleles; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002454:Cell Differentiation; D002490:Central Nervous System / Q000378:metabolism*; D004594:Electrophysiology; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism; D009411:Nerve Endings / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism; D013569:Synapses / Q000502:physiology
chemical_list: C496826:Brsk1 protein, mouse; C496825:Brsk2 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: Calyx of Held; Ia synapse; neuromuscular junction; spinal cord; sympathetic ganglion