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Maosong Qi

Publications and source records attributed to Maosong Qi.

6 recordsLinked to original sources
PubMed2006

Caveolin-1alpha and -1beta perform nonredundant roles in early vertebrate development.

Caveolins are integral membrane proteins that localize predominantly to lipid rafts, where they oligomerize to form flask-shaped organelles termed caveolae and play important roles in membrane trafficking, signal transduction, and other cellular processes. To investigate potential roles for caveolin-1 (cav-1) in development, cav-1alpha and -1beta cDNAs were functionally characterized in the zebrafish. Cav-1alpha and -1beta mRNAs exhibited overlapping but distinct expression patterns throughout embryogenesis. Targeted depletion of either Cav-1 isoform, using antisense morpholino oligomers, resulted in a substantial loss of caveolae and dramatic neural, eye, and somite defects by 12 hours after fertilization, the time at which mRNA levels of both isoforms substantially increased in wild-type animals. Morphant phenotypes were rescued by injection of homotypic (cav-1alpha/cav-1alpha) but not heterotypic (cav-1alpha/cav-1beta) zebrafish and human cav-1 cRNAs, revealing nonredundant and evolutionarily conserved functions for the individual Cav-1 isoforms. Mutation of a known Cav-1 phosphorylation site unique to Cav-1alpha (Y14-->F) resulted in a failure to rescue the cav-1alpha morphant phenotype, verifying an essential role for Cav-1alpha specifically and implicating this residue in early developmental functions. Cav-1alpha and -1beta morphants also exhibited disruption in the actin cytoskeleton. These results support important and previously unanticipated roles for the Caveolin-1 isoforms in vertebrate organogenesis.

Actins↗
PubMed2005

Formin-induced actin cables are required for polarized recruitment of the Ste5 scaffold and high level activation of MAPK Fus3.

Little is known about how a mitogen-activated protein kinase (MAPK) cascade is targeted to specific sites at the plasma membrane during receptor stimulation. In budding yeast, the Ste5 scaffold is recruited to a receptor-coupled G protein during mating pheromone stimulation, allowing the tethered MAPK cascade to be activated by Ste20, a Cdc42-anchored kinase. Here we show that stable recruitment of Ste5 at cortical sites requires the formin Bni1, Bni1-induced actin cables, Rho1 and Myo2. Rho1 directs recruitment of Bni1 via the Rho-binding domain, and Bni1 mediates localization of Ste5 through actin cables and Myo2, which co-immunoprecipitates with Ste5 during receptor stimulation. Bni1 is also required for polarized recruitment and full activation of MAPK Fus3, which must bind Ste5 to be activated, and polarized recruitment of Cdc24, the guanine exchange factor that binds Ste5 and promotes its recruitment to the G protein. In contrast, Bni1 is not important for activation of MAPK Kss1, which can be activated while not bound to Ste5 and does not accumulate at cortical sites. These findings reveal that Bni1 mediates the formation of a Ste5 scaffold/Fus3 MAPK signaling complex at polarized sites, and suggests that a pool of Ste5 may translocate along formin-induced actin cables to the cell cortex.

Actins↗
PubMed2004

Localized feedback phosphorylation of Ste5p scaffold by associated MAPK cascade.

Scaffold proteins play pivotal roles during signal transduction. In Saccharomyces cerevisiae, the Ste5p scaffold protein is required for activation of the mating MAPK cascade in response to mating pheromone and assembles a G protein-MAPK cascade complex at the plasma membrane. To serve this function, Ste5p undergoes a regulated localization event involving nuclear shuttling and recruitment to the cell cortex. Here, we show that Ste5p is also subject to two types of phosphorylation and increases in abundance as a result of MAPK activation. During vegetative growth, Ste5p is basally phosphorylated through a process regulated by the CDK Cdc28p. During mating pheromone signaling, Ste5p undergoes increased phosphorylation by the mating MAPK cascade. Multiple kinases of the mating MAPK cascade contribute to pheromone-induced phosphorylation of Ste5p, with the mating MAPKs contributing the most. Pheromone induction or overexpression of the Ste4p Gbeta subunit increases the abundance of Ste5p at a post-translational step, as long as the mating MAPKs are present. Increasing the level of MAPK activation increases the amount of Ste5p at the cell cortex. Analysis of Ste5p localization mutants reveals a strict requirement for Ste5p recruitment to the plasma membrane for the pheromone-induced phosphorylation. These results suggest that the pool of Ste5p that is recruited to the plasma membrane selectively undergoes feedback phosphorylation by the associated MAPKs, leading to an increased pool of Ste5p at the site of polarized growth. These findings provide evidence of a spatially regulated mechanism for post-activation control of a signaling scaffold that potentiates pathway activation.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Differential input by Ste5 scaffold and Msg5 phosphatase route a MAPK cascade to multiple outcomes.

Pathway specificity is poorly understood for mitogen-activated protein kinase (MAPK) cascades that control different outputs in response to different stimuli. In yeast, it is not known how the same MAPK cascade activates Kss1 MAPK to promote invasive growth (IG) and proliferation, and both Fus3 and Kss1 MAPKs to promote mating. Previous work has suggested that the Kss1 MAPK cascade is activated independently of the mating G protein (Ste4)-scaffold (Ste5) system during IG. Here we demonstrate that Ste4 and Ste5 activate Kss1 during IG and in response to multiple stimuli including butanol. Ste5 activates Kss1 by generating a pool of active MAPKKK (Ste11), whereas additional scaffolding is needed to activate Fus3. Scaffold-independent activation of Kss1 can occur at multiple steps in the pathway, whereas Fus3 is strictly dependent on the scaffold. Pathway specificity is linked to Kss1 immunity to a MAPK phosphatase that constitutively inhibits basal activation of Fus3 and blocks activation of the mating pathway. These findings reveal the versatility of scaffolds and how a single MAPK cascade mediates different outputs.

1-Butanol↗