Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male germ cell differentiation requires a highly cell-specific gene expression programme that is achieved by unique chromatin remodelling, transcriptional control, and the expression of testis-specific genes or isoforms. The regulatory processes governing gene expression in spermatogenesis have fundamentally unique requirements, including meiosis, ongoing cellular differentiation and a peculiar chromatin organization. The signalling cascades and the downstream effectors contributing to the programme of spermatogenesis are currently being unravelled, revealing the unique features of germ cell regulatory circuits. This paper reports on the unique role that CREM exerts as a master regulator. Targeted inactivation of the genes encoding CREM and ACT has been achieved. ACT selectively associates with KIF17b, a kinesin motor protein highly expressed in germ cells. It has been found that KIF17b directly determines the intracellular localization of ACT. Thus, the activity of a transcriptional co-activator is intimately coupled to the function of a kinesin via tight regulation of its intracellular localization. The conservation of these elements and of their regulatory functions in human spermatogenesis indicates that they are likely to provide important insights into understanding the molecular mechanisms of human infertility.
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PMID:Genetic control of spermiogenesis: insights from the CREM gene and implications for human infertility. 1570 96

Macrophages and dendritic cells exposed to lipopolysaccharide (LPS) convert their lysosomes from small, punctate organelles into a network of tubules. Tubular lysosomes have been implicated in phagosome maturation, retention of fluid phase, and antigen presentation. There is a growing appreciation that lysosomes act as sensors of stress and the metabolic state of the cell through the kinase mTOR. Here we show that LPS stimulates mTOR and that mTOR is required for LPS-induced lysosome tubulation and secretion of major histocompatibility complex II in macrophages and dendritic cells. Specifically, we show that the canonical phosphatidylinositol 3-kinase-Akt-mTOR signaling pathway regulates LPS-induced lysosome tubulation independently of IRAK1/4 and TBK. Of note, we find that LPS treatment augmented the levels of membrane-associated Arl8b, a lysosomal GTPase required for tubulation that promotes kinesin-dependent lysosome movement to the cell periphery, in an mTOR-dependent manner. This suggests that mTOR may interface with the Arl8b-kinesin machinery. To further support this notion, we show that mTOR antagonists can block outward movement of lysosomes in cells treated with acetate but have no effect in retrograde movement upon acetate removal. Overall our work provides tantalizing evidence that mTOR plays a role in controlling lysosome morphology and trafficking by modulating microtubule-based motor activity in leukocytes.
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PMID:mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells. 2658 90


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