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Spatial regulation of organelle release from myosin V transport by p21-activated kinases.

ABSTRACT: Correct positioning of organelles is essential to eukaryotic cells. Molecular motors transport organelles to their proper destinations, yet little is known about the pathways that define these destinations. In Saccharomyces cerevisiae, the myosin V motor Myo2 binds the vacuole-specific adapter Vac17 to attach to the vacuole/lysosome and initiate transport. After arrival in the bud, Myo2 releases the vacuole, and Vac17 is degraded. However, the mechanisms that spatially regulate this release were not established. In this study, we report that the bud cortex is a landmark that signals a successful delivery of the vacuole to the bud. We demonstrate that upon arrival at the bud cortex, Vac17 is phosphorylated by Cla4. Cla4-dependent phosphorylation is required for the ubiquitylation and subsequent degradation of Vac17 and the release of the vacuole from Myo2. Our study reveals a critical step in the spatial regulation of myosin V-dependent organelle transport and may reveal common mechanisms for how molecular motors accurately deposit cargoes at the correct locations.

SUBMITTER: Yau RG

PROVIDER: S-EPMC5461012 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Spatial regulation of organelle release from myosin V transport by p21-activated kinases.

Yau Richard G RG Wong Sara S Weisman Lois S LS

The Journal of cell biology 20170511 6

Correct positioning of organelles is essential to eukaryotic cells. Molecular motors transport organelles to their proper destinations, yet little is known about the pathways that define these destinations. In <i>Saccharomyces cerevisiae</i>, the myosin V motor Myo2 binds the vacuole-specific adapter Vac17 to attach to the vacuole/lysosome and initiate transport. After arrival in the bud, Myo2 releases the vacuole, and Vac17 is degraded. However, the mechanisms that spatially regulate this relea ...[more]

PMID: 28495836

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Project description:Microbial infections are most often countered by inflammatory responses that are initiated through the recognition of conserved microbial products by innate immune receptors and result in pathogen expulsion1-6. However, inflammation can also lead to pathology. Tissues such as the intestinal epithelium, which are exposed to microbial products, are therefore subject to stringent negative regulatory mechanisms to prevent signalling through innate immune receptors6-11. This presents a challenge to the enteric pathogen Salmonella Typhimurium, which requires intestinal inflammation to compete against the resident microbiota and to acquire the nutrients and electron acceptors that sustain its replication12,13. We show here that S. Typhimurium stimulates pro-inflammatory signalling by a unique mechanism initiated by effector proteins that are delivered by its type III protein secretion system. These effectors activate Cdc42 and the p21-activated kinase 1 (PAK1) leading to the recruitment of TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase kinase 7 (TAK1), and the stimulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory signalling. The removal of Cdc42, PAK1, TRAF6 or TAK1 prevented S. Typhimurium from stimulating NF-κB signalling in cultured cells. In addition, oral administration of a highly specific PAK inhibitor blocked Salmonella-induced intestinal inflammation and bacterial replication in the mouse intestine, although it resulted in a significant increase in the bacterial loads in systemic tissues. Thus, S. Typhimurium stimulates inflammatory signalling in the intestinal tract by engaging critical downstream signalling components of innate immune receptors. These findings illustrate the unique balance that emerges from host-pathogen co-evolution, in that pathogen-initiated responses that help pathogen replication are also important to prevent pathogen spread to deeper tissues.

Dataset Information

Spatial regulation of organelle release from myosin V transport by p21-activated kinases.

Publications

Spatial regulation of organelle release from myosin V transport by p21-activated kinases.

Similar Datasets

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