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Abstract

Dynamin II interacts with the cadherin- and occludin-based protein complexes at the blood-testis barrier in adult rat testes 
Lie,Pearl P.Y.; Xia,Weiliang; Wang,Claire Q.F.; Mruk,Dolores D.; Yan,Helen H.N.; Wong,Ching-hang; Lee,Will M.; Cheng,Chuen-yan
Journal of Endocrinology 191(3): 571-586
Publication date: 2006


In adult rat testes, blood-testis barrier (BTB) restructuringfacilitates the migration of preleptotene spermatocytes fromthe basal to the adluminal compartment that occurs at stageVIII of the epithelial cycle. Structural proteins at the BTBmust utilize an efficient mechanism (e.g. endocytosis) to facilitateits transient 'opening'. Dynamin II, a large GTPaseknown to be involved in endocytosis, was shown to be a productof Sertoli and germ cells in the testis. It was also localizedto the BTB, as well as the apical ectoplasmic specialization(apical ES), during virtually all stages of the epithelial cycle.By co-immunoprecipitation, dynamin II was shown to associatewith occludin, N-cadherin, zonula occludens-1 (ZO-1), ß-catenin,junctional adhesion molecule-A, and p130Cas, but not nectin-3.An in vivo model in rats previously characterized for studyingadherens junction (AJ) dynamics in the testes by adjudin (formerlycalled AF-2364, 1-(2,4-dichlorobenzyl)-1H-indazole-3-car-hohydrizide)treatment was used in our studies. At the time of germ cellloss from the seminiferous epithelium as a result of adjudin-inducedAJ restructuring without disrupting the BTB integrity, a significantdecline in the steady-state dynamin II protein level was detected.This change was associated with a concomitant increase in thelevels of two protein complexes at the BTB, namely occludin/ZO-1and N-cadherin/ß-catenin. Interestingly, these changeswere also accompanied by a significant increase in the structuralinteraction of dynamin II with ß-catenin and ZO-1.ß-Catenin and ZO-1 are adaptors that structurallylink the cadherin- and occludin-based protein complexes togetherat the BTB in an 'engaged'state to reinforce thebarrier function in normal testes. However, ß-cateninand ZO-1 were 'disengaged' from each other but boundto dynamin II during adjudin-induced AJ restructuring in thetestis. The data reported herein suggest that dynamin II mayassist the 'disengagement' of ß-cateninfrom ZO-1 during BTB restructuring. Thus, this may permit theoccludin/ZO-1 complexes to maintain the BTB integrity when thecadherin/catenin complexes are dissociated to facilitate germcell movement.