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

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

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

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

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 (Ar é valo et al.,2004)

6. ARMS localized at the neuromuscular junction

7. ARMS colocalized with EphA4 and TrkB at the NMJ

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

9. ARMS interacted with  -syntrophin

10. ARMS and syntrophin colocalized in muscle

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

12. Muscle fiber Ephrin EphA4 ARMS Syn ?

13. ARMS interacted with EphA4 receptor

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

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

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

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

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

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