Cyclin-Dependent Kinases Control Septin Phosphorylation in Candida albicans Hyphal Development

Sinha, Indrajit; Wang, Yan Ming; Philp, Robin; Li, Chang-Run; Yap, Wai Ho

doi:10.1016/j.devcel.2007.06.011

Cited by 117 publications

(153 citation statements)

References 43 publications

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“…Scgin4D mutants exhibit similar defects, which are rather milder because of the existence of redundant kinases (Altman and Kellogg, 1997;Barral et al, 1999). We have previously shown that CaGin4 phosphorylates Cdc11 to prime it for further phosphorylation by Cdc28 during hyphal growth (Sinha et al, 2007). These observations indicate that Gin4 plays a conserved role in septin regulation.…”

Section: Introductionmentioning

confidence: 59%

“…Mass spectrometry of immunopurified GFP-Gin4 detected phosphorylation in three perfect (T397, S455 and S467) and four minimal CDK sites (S477, S556, S1217 and T778) among dozens S469, S473, S477 KSMVSDES*S*AS*DDVFDKI S1077, S1078, S1080 RASHIS*VS*RPT*S*FQYKS S407, S409, T412, S413 KSMVS*DES*S*AS*DDVFDKI S1073, S1076, S1077, S1079 KNDYDDT*FVS*NSDEVHKR T1055, S1058 RGNNSSGHDDS*VPPPPPAHKV S1153 KST*KS*S*IDELANGTSTSGHRK T1094, S1096, S1097 KNDADPNNS*EQELVDEGIKQ S719 KNDYDDTFVS*NSDEVHKRQ S1058 RQPSIS*S*S*IMS*QSNHNHPQKI S10, S11, S12, S15 KLLET*SCGSPHYAAPEIVSGLKY T191 RALS*EGNHASEELTLEDVENLKR S745 KSELQDEET*EKNGDGLPYGIERE T69 KLPDGKS*T*KS*S*IDELANGT*STSGHRK S1093, T1094, S1096, S1097, T1105 KYPMSNEDLIS*EKS*LPHPQTGYKS S300, S303 KTIENNTNAATNTTTQQQLPS*PAESKE S1217 RDYELPEPTVEDSNLT*DDYMTEIRK T875 RERDYELPEPT*VEDSNLTDDYMTEIRK T868 KAGLAEPEYET*ET*DGEDKVS*VIDLDDHLADRR T989, T991, S998 RYMIDEPNQPQLQQPALSQVPENPIVDES*PDLMQSAKI S555 { Phosphorylation site mapping by tandem mass spectrometry was carried out as described previously (Sinha et al, 2007). *Asterisks indicate phosphoserine or phosphothreonine residues.…”

Section: Resultsmentioning

confidence: 99%

“…Two other weaker bands were around the sizes of Cdc3 and Nap1; further characterization of which will be published elsewhere. Gin4 phosphorylation of Cdc11 was expected because it was detected previously (Sinha et al, 2007). To confirm Gin4 phosphorylation of Sep7, we repeated the kinase reaction using Gin4-septin complexes purified from a sep7D mutant.…”

Section: Gin4 Phosphorylates Sep7mentioning

confidence: 99%

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CDK Regulates Septin organization through Cell-cycle-dependent Phosphorylation of the Nim1-related Kinase Gin4

Yong

Wang

et al. 2012

Journal of Cell Science

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SummaryCyclin-dependent kinases (CDKs) regulate septin organization in a cell-cycle-dependent manner in yeast. However, the mechanism remains unclear. Here, we show that the Candida albicans CDK Cdc28 phosphorylates the Nim1-related kinase Gin4, a known septin regulator, activating its kinase activity, which in turn phosphorylates the Sep7 septin. Gin4 contains a cluster of CDK phosphorylation sites near the kinase domain. Replacing serine/threonine with alanine in these sites prevents Gin4 activation, weakens its association with Sep7, alters Sep7 dynamics and causes morphological and cytokinetic defects. By contrast, phosphomimetic mutation enhances the kinase activity with only moderate deteriorating effects. We also found that Gin4 has both kinase-independent and -dependent functions, acting during G1 phase and mitosis, respectively, with the former being essential for septin ring assembly. Thus, we have identified a previously unknown signaling pathway linking CDKs and the septins that provides new insights into the mechanisms controlling septin organization and function in coordination with cell-cycle phases.

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Section: Introductionmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Gin4 Phosphorylates Sep7mentioning

confidence: 99%

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CDK Regulates Septin organization through Cell-cycle-dependent Phosphorylation of the Nim1-related Kinase Gin4

Yong

Wang

et al. 2012

Journal of Cell Science

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“…There is strong genetic evidence that Cln1p and Cln2p in particular are needed to promote proper septin ring assembly (Benton et al 1993;Cvrckova et al 1995;Gladfelter et al 2005) and that some septins are direct CDK targets (Tang and Reed 2002;Egelhofer et al 2008), although phosphosite mutants of individual septins did not have any obvious effect on septin ring assembly. In contrast to the inconclusive findings from S. cerevisiae, analogous work in the related Candida albicans provided strong evidence that CDK-mediated septin phosphorylation directly impacts septin organization and hyphal growth (Sinha et al 2007;Gonzalez-Novo et al 2008). Thus, it seems highly likely that CDKs directly regulate septin assembly as well as indirectly promote septin organization through Cdc42p polarization.…”

Section: Polarity Establishment In G1mentioning

confidence: 82%

Morphogenesis and the Cell Cycle

2012

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Studies of the processes leading to the construction of a bud and its separation from the mother cell in Saccharomyces cerevisiae have provided foundational paradigms for the mechanisms of polarity establishment, cytoskeletal organization, and cytokinesis. Here we review our current understanding of how these morphogenetic events occur and how they are controlled by the cellcycle-regulatory cyclin-CDK system. In addition, defects in morphogenesis provide signals that feed back on the cyclin-CDK system, and we review what is known regarding regulation of cell-cycle progression in response to such defects, primarily acting through the kinase Swe1p. The bidirectional communication between morphogenesis and the cell cycle is crucial for successful proliferation, and its study has illuminated many elegant and often unexpected regulatory mechanisms. Despite considerable progress, however, many of the most puzzling mysteries in this field remain to be resolved.

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“…Ccn1p-Cdc28p has been shown to phosphorylate Cdc11p at residue 394 (Sinha et al, 2007). This phosphorylation is dependent on prior phosphorylation at position 395 by the Gin4p kinase.…”

Section: Control Of Vesicle Trafficmentioning

confidence: 99%

Regulation of polarised growth in fungi

Sudbery

2008

Fungal Biology Reviews

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Polarised growth in fungi occurs through the delivery of secretory vesicles along tracks formed by cytoskeletal elements to specific sites on the cell surface where they dock with a multiprotein structure called the exocyst before fusing with the plasmamembrane. The budding yeast, Saccharomyces cerevisiae has provided a useful model to investigate the mechanisms involved and their control. Cortical markers, provided by bud site selection pathways during budding, the septin ring during cytokinesis or the stimulation of the pheromone response receptors during mating, act through upstream signalling pathways to localise Cdc24, the GEF for the rho family GTPase, Cdc42. Cdc42 in its GTP-bound activates a multiprotein protein complex called the polarisome which nucleates actin cables along which the secretory vesicles are transported to the cell surface. Hyphae can elongate at a rate orders of magnitude faster than the extension of a yeast bud, so understanding hyphal growth will require substantial modification of the yeast paradigm.The rapid rate of hyphal growth is driven by a structure called the Spitzenkörper, located just behind the growing tip and which is rich in secretory vesicles. It is thought that secretory vesicles are delivered to the apical region where they accumulate in the Spitzenkörper. The Spitzenkörper then acts as vesicle supply centre in which vesicles exit the Spitzenkörper in all directions, but because of its proximity, the tip receives a greater concentration of vesicles per unit area than subapical regions. There are no obvious equivalents to the bud site selection pathway to provide a spatial landmark for polarised growth in hyphae. However, an emerging model is the way that the site of polarised growth in the fission yeast, Schizosaccharomyces pombe, is marked by delivery of the kelch repeat protein, Tea1, along microtubules. The relationship of the Spitzenkörper to the polarisome and the mechanisms that promote its formation are key questions that form the focus of current research.3

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Cyclin-Dependent Kinases Control Septin Phosphorylation in Candida albicans Hyphal Development

Cited by 117 publications

References 43 publications

CDK Regulates Septin organization through Cell-cycle-dependent Phosphorylation of the Nim1-related Kinase Gin4

CDK Regulates Septin organization through Cell-cycle-dependent Phosphorylation of the Nim1-related Kinase Gin4

Morphogenesis and the Cell Cycle

Regulation of polarised growth in fungi

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