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Fer kinase is a 94 kDa cytoplasmic adherens junction
(AJ)-associated non-receptor protein tyrosine kinase found
in multiple epithelia including the testis, whereas
FerT kinase (51 kDa) is the truncated
testis-specific form of Fer kinase, lacking the
Fps/Fes/Fer/CIP4 and the three coiled-coil (CC) domains
versus Fer kinase. Yet the role(s) of Fer kinase in AJ
dynamics in the testis remains largely unexplored. We
have used an in vitro model of AJ assembly with
Sertoli-germ cell cocultures and an in vivo
model of AJ disassembly in which adult rats were treated
with 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide
(AF-2364) to study changes in the expression and/or
localization of Fer kinase during AJ restructuring. Fer
kinase/FerT was expressed by Sertoli and germ cells
when cultured in vitro. Using an antibody prepared against
a synthetic peptide,
NH2-SAPQNCPEEIFTIMMKCWDYK-COOH,
corresponding to residues 779-799 of Fer kinase, which
failed to cross-react with FerT kinase, for
immunohistochemistry, Fer kinase was detected in the
seminiferous epithelium in virtually all stages of the
cycle. At stages XIII-VI, Fer kinase was associated
largely with round and elongating spermatids. At stages
VII-VIII, Fer kinase associated almost exclusively with
round spermatids with very weak staining associated with
elongated spermatids. This stage-specific localization of
Fer kinase in the epithelium was confirmed by using staged
tubules for semi-quantitative RT-PCR. Studies by
immunoprecipitation revealed that Fer kinase associated
with N-cadherin, 
-catenin, p120ctn,
c-Src, Rab 8, actin, vimentin, but not E-cadherin, afadin,
nectin-3, and integrin , suggesting Fer kinase
associates not only with the actin-based cell-cell AJ
structures, such as the N-cadherin/catenin complex (but
not the 
61 integrin/laminin and the
afadin/nectin complex), but also with intermediate
filament-based cell-cell desmosomes. An induction in Fer
kinase expression was detected during Sertoli-germ cell AJ
assembly in vitro but not during AF-2364-induced AJ
disruption in vivo. Yet this AF-2364-induced Fer kinase
plummeting associated with an induction in N-cadherin,
-catenin, and p120ctn particularly at
the base of the seminiferous epithelium. In summary, Fer
kinase structurally associates with the N-cadherin/catenin
protein complex in the testis and can possibly be used to
mediate signaling function via the cadherin/catenin
protein complex.
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