Mammalian SAD Kinases Are Required for Neuronal Polarization

Electrical activity in neurons is generally initiated in dendritic processes then propagated along axons to synapses, where it is passed to other neurons. Major structural features of neurons—their dendrites and axons—are thus related to their fundamental functions: the receipt and transmission of information. The acquisition of these distinct properties by dendrites and axons, called polarization, is a critical step in neuronal differentiation. We show here that SAD-A and SAD-B, mammalian orthologs of a kinase needed for presynaptic differentiation in Caenorhabditis elegans, are required for neuronal polarization. These kinases will provide entry points for unraveling signaling mechanisms that polarize neurons.

[1]  A. Ashworth,et al.  LKB1 Kinase: Master and Commander of Metabolism and Polarity , 2004, Current Biology.

[2]  B. Lu,et al.  PAR-1 Kinase Plays an Initiator Role in a Temporally Ordered Phosphorylation Process that Confers Tau Toxicity in Drosophila , 2004, Cell.

[3]  O. Marín,et al.  Cell migration in the forebrain. , 2003, Annual review of neuroscience.

[4]  E. Mandelkow,et al.  MARKK, a Ste20‐like kinase, activates the polarity‐inducing kinase MARK/PAR‐1 , 2003, The EMBO journal.

[5]  J. Olavarria,et al.  Beyond Laminar Fate: Toward a Molecular Classification of Cortical Projection/Pyramidal Neurons , 2003, Developmental Neuroscience.

[6]  Y. Jan,et al.  Hippocampal Neuronal Polarity Specified by Spatially Localized mPar3/mPar6 and PI 3-Kinase Activity , 2003, Cell.

[7]  E. Mandelkow,et al.  Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity. , 2002, Molecular biology of the cell.

[8]  A. Wodarz Establishing cell polarity in development , 2002, Nature Cell Biology.

[9]  S. Kaech,et al.  Sorting and directed transport of membrane proteins during development of hippocampal neurons in culture , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Lichtman,et al.  Multicolor “DiOlistic” Labeling of the Nervous System Using Lipophilic Dye Combinations , 2000, Neuron.

[11]  C. Dotti,et al.  The role of local actin instability in axon formation. , 1999, Science.

[12]  M. Ogasawara,et al.  Maternally localized RNA encoding a serine/threonine protein kinase in the ascidian, Halocynthia roretzi , 1998, Mechanisms of Development.

[13]  C Blakemore,et al.  Mechanisms Underlying the Early Establishment of Thalamocortical Connections in the Rat , 1998, The Journal of Neuroscience.

[14]  B. Pettmann,et al.  Neuronal Cell Death , 1998, Neuron.

[15]  G. Drewes,et al.  MARK, a Novel Family of Protein Kinases That Phosphorylate Microtubule-Associated Proteins and Trigger Microtubule Disruption , 1997, Cell.

[16]  J. Mandell,et al.  A Spatial Gradient of Tau Protein Phosphorylation in Nascent Axons , 1996, The Journal of Neuroscience.

[17]  K. Kemphues,et al.  par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed , 1995, Cell.

[18]  G. Brewer,et al.  Optimized survival of hippocampal neurons in B27‐supplemented neurobasal™, a new serum‐free medium combination , 1993, Journal of neuroscience research.

[19]  E. Mandelkow,et al.  Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: Distinction between PHF-like immunoreactivity and microtubule binding , 1993, Neuron.

[20]  K. Kaibuchi,et al.  Role of CRMP-2 in neuronal polarity. , 2004, Journal of neurobiology.

[21]  Cori Bargmann,et al.  The SAD-1 Kinase Regulates Presynaptic Vesicle Clustering and Axon Termination , 2001, Neuron.

[22]  J. Sanes,et al.  Development of the vertebrate neuromuscular junction. , 1999, Annual review of neuroscience.

[23]  G. Banker,et al.  Culturing nerve cells , 1998 .