Type:Protein
SpeciesReactivity:Ch;H
B=Bovine;Ca=Cat;Ch=Chicken;D=Dog;EQ=Equine;GP=GuineaPig;H=Human;M=Mouse;P=Porcine;Pr=Primate;R=Rat;Rb=Rabbit;Y=Yeast;Xe=Xenopus;Ze=Zebrafish;;;;NA-NotApplicable;STP=Step-TactinProteins;All
Slit2isamemberoftheSlitfamilyoflargesecretedaxonguidancemoleculesthatshare6570%aminoacid(aa)identityandareligandsforRoboreceptors(1,2).Similartoothermammalianfamilymembers,the1521aa,~200kDaSlit2containsa25aasignalsequencefollowedbyfourgroupsofleucinerichrepeats(22LRRtotal),9EGFlikesequencesandaCterminalcysteinerichdomain(2).AnALPS(agrinlamininperlecanslit)domainisfoundbetweenEGF6andEGF7(1,2).AproteolyticcleavagesiteoccursbetweenEGF5andEGF6.AmembraneassociationsitejustN-terminaltothecleavagesite,createsamembrane-bound~140kDaN-terminalcleavageproduct(Slit2N)thathaschemorepellentactivity(3).HeparinsulfateisrequiredforinteractionofRobowithSlitLRRdomains(2,4).MaturemouseSlit2shares98,97,97,97and95%aaidentitywithrat,human,bovine,equineandcanineSlit2.
Image:CulturedchickdorsalrootganglionneuronsweregrowninthepresenceofrecombinanthumanNGF-bwith(A)orwithout(B)recombinantmouseSlit2.ThepresenceoftheSlit2proteinsignificantlyenhancedneuriteoutgrowth.
Slit1andSlit2(orinsomecasesSlit3)areexpressedincomplementarylocationsduringdevelopmentoftheopticandolfactorytractsandtheforebrain,andappeartoworktogethertomediateRoboguidanceofretinal,olfactory,hippocampalandmotoraxons(1,59).DeletionofeitherSlit1orSlit2haslesseffectthandeletionofboth,whichallowsaxonstowanderfromtractsandinappropriatelycrossorrecrossthemidline(79).Slit2alsofunctionsoutsidethenervoussystemtoinhibitmigrationofleukocytes,endothelialcellsandvascularsmoothmusclecellstowardCXCL12/SDF1,VEGF165andPDGF,respectively(3,10,11).SlitsandRobosareconsideredcandidatetumorsuppressorgenesbecausetheirpromotorsarefrequentlyhypermethylatedinepithelialcancers(12).LossofSlit2andSlit3expressionearlyduringtumorprogressionupregulatesakeychemokinesignalingaxisandgenerateshyperplasticchangesintheepitheliumalongwithdesmoplasticchangesinthestroma(13).
