Regulation of nuclear import during differentiation: The IMP alpha gene family and spermatogenesis

Access to nuclear genes in eukaryotes is provided by members of the importin (IMP) superfamily of proteins, which are of alpha- or beta-types, the best understood nuclear import pathway being mediated by a heterodimer of an IMP alpha and IMP beta1. IMP alpha recognises specific targeting signals on cargo proteins, while IMP beta1 mediates passage into, and release within, the nucleus by interacting with other components of the transport machinery, including the monomeric guanine nucleotide binding protein Ran. In this manner, hundreds of different proteins can be targeted specifically into the nucleus in a tightly regulated fashion. The IMP alpha gene family has expanded during evolution, with only a single IMP alpha (Srp1p) gene in budding yeast, and three (IMP alpha1, 2/pendulin and 3) and five (IMP alpha1, -2, -3, -4 and -6) IMP alpha genes in Drosophila melanogaster and mouse respectively, which fall into three phylogenetically distinct groups. The fact that IMP alpha3 and IMP alpha2 are only present in metazoans implies that they emerged during the evolution of multicellular animals to perform specialised roles in particular cells and tissues. This review describes what is known of the IMP alpha gene family in mouse and in D. melanogaster, including a comparitive examination of their mRNA expression profiles in a highly differentiated tissue, the testis. The clear implication of their highly regulated synthesis during the course of spermatogenesis is that the different IMP alphas have distinct expression patterns during cellular differentiation, implying tissue/cell type-specific roles.