ABSTRACT
The formation of the nervous systems requires processes that coordinate proliferation, differentiation and migration of neuronal cells, which extend axons, generate dendritic branching and establish synaptic connections during development. The structural organization and dynamic remodeling of the cytoskeleton and its association to the secretory pathway are critical determinants of cell morphogenesis and migration. Marlin-1 (Jakmip1) is a microtubule-associated protein predominantly expressed in neurons and lymphoid cells. Marlin-1 participates in polarized secretion in lymphocytes, but its functional association with the neuronal cytoskeleton and its contribution to brain development have not been explored. Combining in vitro and in vivo approaches we show that Marlin-1 contributes to the establishment of neuronal morphology. Marlin-1 associates to the cytoskeleton in neurites, is required for the maintenance of an intact Golgi apparatus and its depletion produces the down-regulation of kinesin-1, a plus-end directed molecular motor with a central function in morphogenesis and migration. RNA interference of Marlin-1 in vivo results in abnormal migration of newborn pyramidal neurons during the formation of the cortex. Our results support the involvement of Marlin-1 in the acquisition of the complex architecture and migration of pyramidal neurons, two fundamental processes for the laminar layering of the cortex.
Subject(s)
Cell Movement , Neurogenesis , Pyramidal Cells/embryology , RNA-Binding Proteins/physiology , Animals , Cell Movement/genetics , Cytoskeleton/metabolism , Female , Golgi Apparatus/metabolism , Kinesins/metabolism , Mice , Mice, Inbred BALB C , Neurogenesis/genetics , Pyramidal Cells/metabolism , RNA Interference , RNA-Binding Proteins/antagonists & inhibitors , RNA-Binding Proteins/genetics , Rats , Rats, Sprague-DawleyABSTRACT
Protein kinase CK2 is a serine/threonine kinase expressed in organisms from yeast to human and is composed of a catalytic subunit (alpha or alpha') and a regulatory subunit (beta) forming a holoenzyme with the possible subunit combinations alpha(2)beta(2), alpha'(2)beta(2), or alphaalpha'beta(2). This kinase has been shown to be involved in embryonic development and gametogenesis. We have studied the expression of the CK2alpha' and CK2beta subunits during the first wave of spermatogenesis and in adult testis in the rat. Western blot analyses have demonstrated that both CK2alpha' and CK2beta are expressed in testes from birth to adulthood. A more detailed study of the protein localization of CK2alpha' and CK2beta by immunohistochemistry suggests that CK2alpha' and CK2beta are localized in the nuclei of Sertoli cells in 5-day-old rats, whereas they appear to have a cytoplasmic localization in older animals. In adult testes, CK2alpha' and CK2beta subunits are present in spermatocytes. Both subunits exhibit a similar expression pattern with the highest level in spermatocytes at stages VIII-XIV. Interestingly, CK2beta is highly expressed in spermatogonia, whereas CK2alpha' is barely detectable. Mature epididymal spermatozoa express CK2alpha' in the acrosome and CK2beta in the flagellum. This new evidence therefore indicates that protein kinase CK2 has a possible role at various stages during mammalian spermatogenesis, a process that involves proliferation, meiosis, apoptosis, and differentiation. CK2 might thus emerge as a new pivotal control enzyme at various levels in mammalian spermatogenesis.
