The transcriptional activator CREM is essential for spermatogenesis, as it regulates the activity of several post-meiotic genes. ACT binds to CREM and functions as its transcriptional coactivator. While investigating the CREM–ACT activation mechanism, Paolo Sassone-Corsi and colleagues found an unexpected player — KIF17b, a testis-specific member of the kinesin family of microtubular motor proteins — as they now report in Science.

Using full-length ACT as bait, Sassone-Corsi and co-workers identified KIF17b — an isoform of the brain-specific kinesin KIF17 — in a yeast two-hybrid assay. They showed that KIF17b is highly, and exclusively, expressed in testis, and that KIF17b and ACT are co-expressed during testis development. The KIF17b–ACT interaction was strong in vitro, and also in vivo, as the proteins present in mouse testis extract co-immunoprecipitated.

Knowing that ACT and most kinesins are localized in the nucleus and cytoplasm, respectively, Sassone-Corsi and co-workers examined the intracellular localization of both proteins at different stages of spermatid development. Although ACT is indeed nuclear, it becomes more cytoplasmic at a specific point during spermatid maturation, which coincides with ACT depletion from the nucleus. The same dual localization pattern was observed for KIF17b at this stage. In COS and NIH3T3 cells transfected with KIF17b and ACT constructs, there was total colocalization of the co-expressed proteins. In most cells, the proteins were cytoplasmic, and in others, they were nuclear and cytoplasmic. These data implied that KIF17b might have a nuclear export activity that regulates the intracellular localization of ACT.

So, does KIF17b have a role in nuclear shuttling? To address this question, KIF17- and ACT-transfected cells were treated with leptomycin B (LMB), which disables the nuclear export receptor Crm1. In treated cells, KIF17b was sequestered in the nucleus, indicating that KIF17b can be actively transported from the nucleus to the cytoplasm through the Crm1 receptor.

Next, Sassone-Corsi and colleagues assayed two CREM-dependent promoter–reporter constructs for transcriptional activity in the presence of ACT and different doses of KIF17b. As KIF17b is responsible for ACT depletion from the nucleus, it did not come as a surprise that transcriptional activation was inhibited in the presence of excess KIF17b. ACT-dependent transcriptional activation could subsequently be recovered by sequestering ACT–KIF17b in the nucleus using LMB treatment.

Together, these data provide the first evidence for a direct functional connection between a microtubular transporter protein and transcriptional regulation.