Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proteins Msb3p (Ynl293p) and Msb4p (Yol112p) of the yeast Saccharomyces cerevisiae are very similar in sequence and share a highly conserved domain called TBC. To characterize the cellular functions of these proteins, we constructed single and double yeast mutants by disrupting the MSB3 gene, the MSB4 gene, or both. Co-deletion of the MSB3 and MSB4 coding regions caused growth inhibition in the presence of 10 mM caffeine and 4% dimethyl sulphoxide (DMSO), increased the sensitivity of the yeast strain to latrunculin-A, produced a random budding pattern in diploid cells, and affected the organization of the actin cytoskeleton. Caffeine sensitivity is often associated with defects in mitogen-activated protein (MAP) kinase pathways, highly conserved mechanisms mediating transduction of external signals. The biological effect of DMSO in S. cerevisiae is unclear. The msb3 msb4 mutant's increased sensitivity to latrunculin-A suggests that the double mutation causes destabilization of the actin cytoskeleton. Microscopic observations confirmed this: in haploid and diploid msb3 msb4 mutant cells, polymerized actin was delocalized from the budding sites. Complementation studies suggested that MSB3 and MSB4 encode overlapping activities in the yeast cells. We thus propose that both Msb3p and Msb4p act in budding site selection, probably via their involvement in the organization of the actin cytoskeleton.
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PMID:Co-deletion of the MSB3 and MSB4 coding regions affects bipolar budding and perturbs the organization of the actin cytoskeleton. 1092 23

The blood-testis barrier (BTB) in mammals, such as rats, is composed of the tight junction (TJ), the basal ectoplasmic specialization (basal ES), the basal tubulobulbar complex (basal TBC) (both are testis-specific actin-based adherens junction [AJ] types), and the desmosome-like junction that are present side-by-side in the seminiferous epithelium. The BTB physically divides the seminiferous epithelium into basal and apical (or adluminal) compartments, and is pivotal to spermatogenesis. Besides its function as an immunological barrier to segregate the postmeiotic germ-cell antigens from the systemic circulation, it creates a unique microenvironment for germ-cell development and confers cell polarity. During spermatogenesis, the BTB in rodents must physically disassemble to permit the passage of preleptotene and leptotene spermatocytes. This occurs at late stage VII through early stage VIII of the epithelial cycle. Studies have shown that this dynamic BTB restructuring to facilitate germ-cell migration is regulated by two cytokines, namely transforming growth factor-beta3 (TGF-beta3) and tumor necrosis factor-alpha (TNFalpha), via downstream mitogen-activated protein kinases. These cytokines determine the homeostasis of TJ- and basal ES-structural proteins, proteases, protease inhibitors, and other extracellular matrix (ECM) proteins (e.g., collagen) in the seminiferous epithelium. Some of these molecules are known regulators of focal contacts between the ECM and other actively migrating cells, such as macrophages, fibroblasts, or malignant cells. These findings also illustrate that cell-cell junction restructuring at the BTB is regulated by mechanisms involved in the junction turnover at the cell-matrix interface. This review critically discusses these latest findings in the field in light of their significance in the biology and regulation of the BTB pertinent to spermatogenesis.
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PMID:The blood-testis barrier: its biology, regulation, and physiological role in spermatogenesis. 1634 8