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ARMS interacts with a -syntrophin: implications for EphA4 signaling at the neuromuscular synapse

ARMS interacts with a -syntrophin: implications for EphA4 signaling at the neuromuscular synapse. Yu CHEN Department of Biochemistry Hong Kong University of Science and Technology. CNS synapse Neuromuscular junction. Pre-synaptic Neuron. Pre-synaptic Motor Neuron.

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ARMS interacts with a -syntrophin: implications for EphA4 signaling at the neuromuscular synapse

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  1. ARMS interacts with a-syntrophin: implications for EphA4 signaling at the neuromuscular synapse Yu CHEN Department of Biochemistry Hong Kong University of Science and Technology

  2. CNS synapse Neuromuscular junction Pre-synaptic Neuron Pre-synaptic Motor Neuron Acetylcholine Schwann cell Acetylcholine receptor Neurotransmitter Ion Influx Neurotransmitter receptor Post-synaptic Neuron Sub-synaptic nucleus Post-synaptic Muscle

  3. Plasma membrane Neuronal survival and differentiation Axon & dendritic growth Axon guidance and neuronal migration ERK Synapse formation and plasticity Nerve regeneration Functions of receptor tyrosine kinases Trophic factors RTK P Raf MEK ERK Nucleus Elk-1 c-Fos

  4. BDNF Ephrin EphA4 TrkB Muscle fiber AChR clustering and NMJ stability Development/maturation of NMJ

  5. ARMS (ankyrin repeat- rich membrane spanning) ● Activation of Eph receptor results in the rapid tyrosine phosphorylation of ARMS (Kong et al.,2001) ● ARMS interacts with TrkB and potentiates TrkB-mediated sustained MAPK activation (Arévalo et al.,2004)

  6. ARMS localized at the neuromuscular junction

  7. ARMS colocalized with EphA4 and TrkB at the NMJ

  8. 1616 1715 EERESIL PH1a PDZ PH1b PH2 SU PH1a PDZ PH1b PH2 SU GI->AA Library screening for ARMS interacting proteins Bait: C-terminal 100 amino acids of ARMS Library: P12 mouse muscle cDNA library ARMS + a-syntrophin a-syntrophin mutant ―

  9. ARMS interacted with a-syntrophin

  10. ARMS and syntrophin colocalized in muscle

  11. ARMS PDZ binding motif and a-syntrophin PDZ domain were necessary for ARMS clustering

  12. Ephrin EphA4 ARMS ? Muscle fiber Syn

  13. ARMS interacted with EphA4 receptor

  14. ? JAK JAK ? Ephrin EphA4 ARMS Muscle fiber Syn STAT Subsynaptic gene transcription

  15. ARMS and a-syntrophin potentiates EphA4-mediated signaling

  16. JAK JAK Ephrin EphA4 ARMS Muscle fiber ? ? Syn STAT Subsynaptic gene transcription

  17. Junctional localization of ARMS was aberrant in syntrophin knockout mice

  18. Junctional localization of EphA4 was aberrant in syntrophin knockout mice

  19. JAK JAK Ephrin EphA4 ARMS Muscle fiber Syn STAT Subsynaptic gene transcription

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