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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelin is organized in subdomains with distinct protein and lipid composition. How these domains are established and maintained is currently unknown. Cytoskeletal elements interacting with membrane components could generate and sustain such structural domains. Here, we demonstrate that the transmembrane myelin protein MAL interacts with the cytoskeleton protein septin 6. Septins represent a fourth filamentous system involved in membrane compartmentalization, vesicle transport and scaffold formation. We report that multiple septin complexes are associated with myelin, and that they display an overlapping but non-identical composition in the central and peripheral nervous system. The expression of distinct subsets of septins was upregulated during myelin formation in peripheral nerves and oligodendrocytes. In the PNS, septins were highly enriched in non-compact myelin compartments, particularly in the paranodal loops and the microvilli at the node of Ranvier. Importantly in myelin lacking Septin 6, the abundance of its closest homolog Sept11 was increased, suggesting a functional compensatory role. Our data demonstrate that the septin cytoskeleton is an integral component of the myelin sheath and interacts with distinct myelin constituents such as MAL. We suggest that septins are intriguing candidates for membrane compartmentalization in myelin internodes.
Mol Cell Neurosci 2009 Feb
PMID:The septin cytoskeleton in myelinating glia. 1902 47

Ni-NTA affinity chromatography under denaturing conditions has proven to be a powerful method for the isolation of SUMO conjugates from total cell extracts, as it minimizes deconjugation and excludes noncovalent interactions. This chapter describes the use of both His-tagged SUMO and a His-tagged target protein for the characterization of the sumoylation process in the budding yeast Saccharomyces cerevisiae. Two well-studied model substrates, the septin Cdc3 and the replication clamp protein PCNA, are used as examples, but the protocol can easily be adapted to other targets and organisms.
Methods Mol Biol 2009
PMID:In vivo detection and characterization of sumoylation targets in Saccharomyces cerevisiae. 1910 12

Cell shape can influence cell behavior. In Saccharomyces cerevisiae, bud emergence can influence cell cycle progression via the morphogenesis checkpoint. This surveillance pathway ensures that mitosis always follows bud formation by linking degradation of the mitosis-inhibitory kinase Swe1p (Wee1) to successful bud emergence. A crucial component of this pathway is the checkpoint kinase Hsl1p, which is activated upon bud emergence and promotes Swe1p degradation. We have dissected the large nonkinase domain of Hsl1p by using evolutionary conservation as a guide, identifying regions important for Hsl1p localization, function, and regulation. An autoinhibitory motif restrains Hsl1p activity when it is not properly localized to the mother-bud neck. Hsl1p lacking this motif is active as a kinase regardless of the assembly state of cytoskeletal septin filaments. However, the active but delocalized Hsl1p cannot promote Swe1p down-regulation, indicating that localization is required for Hsl1p function as well as Hsl1p activation. We also show that the septin-mediated Hsl1p regulation via the novel motif operates in parallel to a previously identified Hsl1p activation pathway involving phosphorylation of the Hsl1p kinase domain. We suggest that Hsl1p responds to alterations in septin organization, which themselves occur in response to the local geometry of the cell cortex.
Mol Biol Cell 2009 Apr
PMID:Molecular dissection of the checkpoint kinase Hsl1p. 1921 41

Septins are conserved, GTP-binding proteins that assemble into higher order structures, including filaments and rings with varied cellular functions. Using four-dimensional quantitative fluorescence microscopy of Ashbya gossypii fungal cells, we show that septins can assemble into morphologically distinct classes of rings that vary in dimensions, intensities, and positions within a single cell. Notably, these different classes coexist and persist for extended times, similar in appearance and behavior to septins in mammalian neurons and cultured cells. We demonstrate that new septin proteins can add through time to assembled rings, indicating that septins may continue to polymerize during ring maturation. Different classes of rings do not arise from the presence or absence of specific septin subunits and ring maintenance does not require the actin and microtubule cytoskeletons. Instead, morphological and behavioral differences in the rings require the Elm1p and Gin4p kinases. This work demonstrates that distinct higher order septin structures form within one cell because of the action of specific kinases.
Mol Biol Cell 2009 Apr
PMID:Regulation of distinct septin rings in a single cell by Elm1p and Gin4p kinases. 1922 52

The septin family is a conserved GTP-binding protein family and was originally discovered through genetic screening for budding yeast mutants. Septins are implicated in many cellular processes in fungi and metazoa. The function of septins usually depends on septin assembling into oligomeric complexes and highly ordered polymers. The expansion of the septin gene number in vertebrates increased the complex diversity of septins. In this review, we first discuss the evolution, structures and assembly of septin proteins in yeast and metazoa. Then, we review the function of septin proteins in cytokinesis, membrane remodeling and compartmentalization.
Cell Mol Life Sci 2009 Oct
PMID:The evolution, complex structures and function of septin proteins. 1959 64

Recent studies have revealed the detailed timing of protein recruitment to endocytic sites in budding yeast. However, little is understood about the early stages of their formation. Here we identify the septin-associated protein Syp1p as a component of the machinery that drives clathrin-mediated endocytosis in budding yeast. Syp1p arrives at endocytic sites early in their formation and shares unique dynamics with the EH-domain protein Ede1p. We find that Syp1p is related in amino acid sequence to several mammalian proteins one of which, SGIP1-alpha, is an endocytic component that binds the Ede1p homolog Eps15. Like Syp1p, SGIP1-alpha arrives early at sites of clathrin-mediated endocytosis, suggesting that Syp1p/Ede1p and SGIP1-alpha/Eps15 may have a conserved function. In yeast, both Syp1p and Ede1p play important roles in the rate of endocytic site turnover. Additionally, Ede1p is important for endocytic site formation, whereas Syp1p acts as a polarized factor that recruits both Ede1p and endocytic sites to the necks of emerging buds. Thus Ede1p and Syp1p are conserved, early-arriving endocytic proteins with roles in the formation and placement of endocytic sites, respectively.
Mol Biol Cell 2009 Nov
PMID:Early-arriving Syp1p and Ede1p function in endocytic site placement and formation in budding yeast. 1977 51

The dimorphic phytopathogenic fungus Ustilago maydis grows in its haploid phase by budding. Cytokinesis and separation of daughter cells are accomplished by the consecutive formation of two distinct septa. Here, we show that both septation events involve the dynamic rearrangement of septin assemblies from hourglass-shaped collars into ring-like structures. Using a chemical genetic approach we demonstrate that the germinal centre kinase Don3 triggers this septin reorganization during secondary septum formation. Although chemical inhibition of an analogue-sensitive version of Don3 prevented septation, a stable septin collar was assembled at the presumptive septation site. Interestingly, the essential light chain of type II myosin, Cdc4, was already associated with this septin collar. Release of Don3 kinase inhibition triggered immediate dispersal of septin filaments and concomitant incorporation of Cdc4 into a contractile actomyosin ring, which also contained the F-BAR domain protein Cdc15. Inhibition of actin polymerization or deletion of the cdc15 gene, did not affect assembly of the initial collar consisting of septin and myosin light chain. However, reassembly of septin filaments into a ring-like structure was prevented in the absence of either F-actin or Cdc15, indicating that septin ring formation in U. maydis depends on a functional contractile actomyosin ring.
Mol Microbiol 2009 Dec
PMID:The germinal centre kinase Don3 triggers the dynamic rearrangement of higher-order septin structures during cytokinesis in Ustilago maydis. 1990 82

Septins are conserved, cytoskeletal GTPases that contribute to cytokinesis, exocytosis, cell surface organization and vesicle fusion by mechanisms that are poorly understood. Roles of septins in morphogenesis and virulence of a human pathogen and basidiomycetous yeast Cryptococcus neoformans were investigated. In contrast to a well-established paradigm in S. cerevisiae, Cdc3 and Cdc12 septin homologues are dispensable for growth in C. neoformans yeast cells at 24 degrees C but are essential at 37 degrees C. In a bilateral cross between septin mutants, cells fuse but the resulting hyphae exhibit morphological abnormalities, including lack of properly fused specialized clamp cells and failure to produce spores. Interestingly, post-mating hyphae of the septin mutants have a defect in nuclear distribution. Thus, septins are essential for the development of spores, clamp cell fusion and also play a specific role in nuclear dynamics in hyphae. In the post-mating hyphae the septins localize to discrete sites in clamp connections, to the septa and the bases of the initial emerging spores. Strains lacking CDC3 or CDC12 exhibit significantly reduced virulence in a Galleria mellonella model of infection. Thus, C. neoformans septins are vital to morphology of the hyphae and contribute to virulence.
Mol Microbiol 2010 Feb
PMID:Septins enforce morphogenetic events during sexual reproduction and contribute to virulence of Cryptococcus neoformans. 1994 2

The precise regulation of morphogenesis is a key mechanism by which cells respond to a variety of stresses, including those encountered by microbial pathogens in the host. The polarity protein Cdc42 regulates cellular morphogenesis throughout eukaryotes, and we explore the role of Cdc42 proteins in the host survival of the human fungal pathogen Cryptococcus neoformans. Uniquely, C. neoformans has two functional Cdc42 paralogues, Cdc42 and Cdc420. Here we investigate the contribution of each paralogue to resistance to host stress. In contrast to non-pathogenic model organisms, C. neoformans Cdc42 proteins are not required for viability under non-stress conditions but are required for resistance to high temperature. The paralogues play differential roles in actin and septin organization and act downstream of C. neoformans Ras1 to regulate its morphogenesis sub-pathway, but not its effects on mating. Cdc42, and not Cdc420, is upregulated in response to temperature stress and is required for virulence in a murine model of cryptococcosis. The C. neoformans Cdc42 proteins likely perform complementary functions with other Rho-like GTPases to control cell polarity, septin organization and hyphal transitions that allow survival in the environment and in the host.
Mol Microbiol 2010 Feb
PMID:Two CDC42 paralogues modulate Cryptococcus neoformans thermotolerance and morphogenesis under host physiological conditions. 2002 59

During yeast sporulation, a forespore membrane (FSM) initiates at each spindle-pole body and extends to form the spore envelope. We used Schizosaccharomyces pombe to investigate the role of septins during this process. During the prior conjugation of haploid cells, the four vegetatively expressed septins (Spn1, Spn2, Spn3, and Spn4) coassemble at the fusion site and are necessary for its normal morphogenesis. Sporulation involves a different set of four septins (Spn2, Spn5, Spn6, and the atypical Spn7) that does not include the core subunits of the vegetative septin complex. The four sporulation septins form a complex in vitro and colocalize interdependently to a ring-shaped structure along each FSM, and septin mutations result in disoriented FSM extension. The septins and the leading-edge proteins appear to function in parallel to orient FSM extension. Spn2 and Spn7 bind to phosphatidylinositol 4-phosphate [PtdIns(4)P] in vitro, and PtdIns(4)P is enriched in the FSMs, suggesting that septins bind to the FSMs via this lipid. Cells expressing a mutant Spn2 protein unable to bind PtdIns(4)P still form extended septin structures, but these structures fail to associate with the FSMs, which are frequently disoriented. Thus, septins appear to form a scaffold that helps to guide the oriented extension of the FSM.
Mol Cell Biol 2010 Apr
PMID:Role of septins in the orientation of forespore membrane extension during sporulation in fission yeast. 2012 72


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