Study On The Interaction Of CRMP1 In Semaphorin Signaling Pathway

In the developing nervous system,axonal guidance cue Sema3 A activates the specific receptor complex neuropilin1 and PlexinA1,then transduces the signal to downstream effectors such as FARPs,CRMPs etc.,to guide the direction of axon through regulation of cytoskeletal reorganization.Furthermore,PlexinA1 interacts with FARPs and CRMPs.CRMPs(Collapsin response mediator proteins),are highly expressed in nervous system,and also involved in cancer invasion and metastasis.CRMP1 serves as a supressor in lung cancer invasion and metastasis.Transfection of CRMP1 gene into highly invasive lung cancer cells can effectively reduce the invasion of cells,but its mechanism is still unknown.We identified the interaction partners of CRMP1 in lung adenocarcinoma cell line A549 by pulldown assay.According to the resaults of mass spectra,CRMP1 may interact with a variety of cancer related proteins,such as keratin,hornerin,dermcidin directly or indirectly,and this would give us a direction for further studying the mechanism of CRMP1.Also,we detected that FARPs,the downstream proteins of Sema3 A signaling pathway,interacted with CRMP1 directly through its FERM domain in vitro.Based on the interaction study of the different truncations and mutants of CRMP1 with FERM domain,we further identified the interaction region of CRMP1,and also found the constitutively active mutant CRMP1-49-56 A interacted with FARP2-FERM more intensively.According to this result,we hypothesized PlexinA1 may mediate the interplay of CRMP1 and FARP2,which might shed light on the molecular mechanism of CRMP1 in Sema 3A pathway.