Secretory Vesicles Deliver Cdc42p to Sites of Polarized Growth in S. cerevisiae

Dighe, Shubha; Kozminski, Keith G.

doi:10.1371/journal.pone.0099494

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…This suggests that either there is some active mechanism for increasing the concentration of signaling molecules in the membrane following vesicle fusion, or some other factor is transported by vesicles that maintains cell polarization. Interestingly, experimental evidence for the former mechanism has recently been obtained by establishing that vesicles deliver Cdc42 to sites of polarized growth in yeast [9]. In this paper, we relax both assumptions (i) and (ii) and show that a more biophysically realistic model of active vesicular transport in the cytoplasm leads to an advection-diffusion equation with anisotropic and space-dependent diffusion.…”

Section: Introductionmentioning

confidence: 77%

“…A dynamic equilibrium of recycling can be maintained only if endocytic vesicles also have an enhanced concentration of signaling molecules. There are various active mechanisms for enhancing the concentration of proteins within vesicles, and although evidence for such processes within the context of cell polarization is currently lacking, it has recently been observed that vesicles do indeed deliver Cdc42 to sites of polarized growth in yeast [9]. We will ignore these issues here and simply assume that each vesicle contains n ves signaling molecules and the membrane concentration increases/decreases by an amount γn ves given a unit flux of vesicles undergoing exo/endocytosis.…”

Section: Deterministic Modelmentioning

confidence: 99%

“…In conclusion, the effects of cytoskeletal geometry on cell polarization identified in [15] persist when biophysical details regarding motor-driven vesicular transport are taken into account. One outstanding challenge is to understand how the vesicular transport of signaling proteins such as Cdc42 [9] can enhance the membrane-bound concentration of the proteins. This will require a more detailed model of the fusion and budding of vesicles with the cell membrane.…”

Section: Case (Ii)mentioning

confidence: 99%

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Stochastic Active-Transport Model of Cell Polarization

Bressloff¹,

Xu²

2015

SIAM J. Appl. Math.

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We present a stochastic model of active vesicular transport and its role in cell polarization, which takes into account positive feedback between membrane-bound signaling molecules and cytoskeletal filaments. In particular, we consider the cytoplasmic transport of vesicles on a two-dimensional cytoskeletal network, in which a vesicle containing signaling molecules can randomly switch between a diffusing state and a state of directed motion along a filament. Using a quasi-steady-state analysis, we show how the resulting stochastic hybrid system can be reduced to an advection-diffusion equation with anisotropic and space-dependent diffusivity. This equation couples to a reaction-diffusion equation for the membrane-bound transport of signaling molecules. We use linear stability analysis to derive conditions for the growth of a precursor pattern for cell polarization, and we show that the geometry of the cytoskeletal filaments plays a crucial role in determining whether the cell is capable of spontaneous cell polarization or only polarizes in response to an external chemical gradient. As previously found in a simpler deterministic model with uniform and isotropic diffusion, the former occurs if filaments are nucleated at sites on the cell membrane (cortical actin), whereas the latter applies if the filaments nucleate from organizing sites within the cytoplasm (microtubule asters). This is consistent with experimental data on cell polarization in two distinct biological systems, namely, budding yeast and neuronal growth cones. Our more biophysically detailed model of motor transport allows us to determine how the conditions for spontaneous cell polarization depend on motor parameters such as mean speed and the rate of unbinding from filament tracks.

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Section: Introductionmentioning

confidence: 77%

Section: Deterministic Modelmentioning

confidence: 99%

Section: Case (Ii)mentioning

confidence: 99%

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Stochastic Active-Transport Model of Cell Polarization

Bressloff¹,

Xu²

2015

SIAM J. Appl. Math.

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“…It, thus, seems that Cdc42 activated at the Golgi membranes downstream of GM130 replenishes the PM pool of active Cdc42 required for directional cell migration and maintenance of cell polarity. Indeed, in fission yeast, active Cdc42 is present on secretory vesicles and delivered to sites of polarized growth [80]. Likewise, in mammalian cells, Cdc42 has been detected on Arf6-positive intracellular vesicles, which are trafficked en route to the leading edge of migration cells [55].…”

Section: Rho Gtpases Acting Along the Secretory Pathwaymentioning

confidence: 99%

Spatiotemporal Control of Intracellular Membrane Trafficking by Rho GTPases

Noll

Haußer

2019

Cells

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As membrane-associated master regulators of cytoskeletal remodeling, Rho GTPases coordinate a wide range of biological processes such as cell adhesion, motility, and polarity. In the last years, Rho GTPases have also been recognized to control intracellular membrane sorting and trafficking steps directly; however, how Rho GTPase signaling is regulated at endomembranes is still poorly understood. In this review, we will specifically address the local Rho GTPase pools coordinating intracellular membrane trafficking with a focus on the endo-and exocytic pathways. We will further highlight the spatiotemporal molecular regulation of Rho signaling at endomembrane sites through Rho regulatory proteins, the GEFs and GAPs. Finally, we will discuss the contribution of dysregulated Rho signaling emanating from endomembranes to the development and progression of cancer.an inactive GDP-bound and an active GTP-bound state. Rho GDP/GTP cycling is tightly regulated by guanine nucleotide exchange factors (GEFs) that promote the formation of the active GTP-bound form through exchanging GDP for GTP. On the contrary, GTPase-activating proteins (GAPs) catalyze the intrinsic GTPase activity and promote the formation of inactive GDP-bound Rho. This inactive state can be subsequently recognized by guanine nucleotide dissociation inhibitors (GDIs), which sequester Rho GTPases in the cytosol [5,6] (Figure 1). Whereas classical Rho GTPases are regulated by GDP/GTP cycling, atypical Rho GTPases are regulated by other mechanisms that occur in particular at the transcriptional and post-translational level [7]. In the case of atypical Rho GTPases, GTP is usually constitutively bound, either because these Rho GTPases possess high intrinsic nucleotide exchange activity or have substitutions in their GTPase domain that prevent GTP hydrolysis.

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“…Additionally, the specific requirement for Osh protein function in polarized exocytosis could be that it facilitates Cdc42p localization at the bud tip of small and medium sized buds (Kozminski et al, 2006;Dighe and Kozminski 2014). Cdc42p…”

Section: Is Sterol or Ps Transfer By Orps Essential?mentioning

confidence: 99%

Members of the OSBP Homologue (Osh) Protein Family in S. cerevisiae Require Specific Lipids to Regulate Polarized Exocytosis

Smindak¹

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The Oxysterol Binding Proteins (OSBPs) are an evolutionarily conserved protein family in eukaryotes implicated in many cellular functions. One function, supported by a large body of in vitro data is lipid transfer between membranes. In addition, in vivo changes in lipid distribution among cellular membranes have been shown to be OSBP dependent, further suggesting a role for OSBPs in lipid homeostasis. Despite these Section 1: Polarized Exocytosis 1 Exocytosis in S. cerevisiae 2 Polarized Exocytosis 5 Lipids Involved in Polarized Exocytosis Membrane-Membrane Contact Section 2: What Essential Functions are Provided by the Oxysterol Binding Proteins? Oxysterol Binding Protein Structure OSBPs in Human Disease Lipid Binding and Transfer Activity of the OSBPs Other Functions of the Oxysterol Binding Protein Family Oxysterol Binding Protein Activity in Polarized Exocytosis iii Chapter 2: Lipid-Dependent Regulation of Exocytosis in S. cerevisiae by OSBP Homologue (Osh) 4

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Secretory Vesicles Deliver Cdc42p to Sites of Polarized Growth in S. cerevisiae

Cited by 7 publications

References 38 publications

Stochastic Active-Transport Model of Cell Polarization

Stochastic Active-Transport Model of Cell Polarization

Spatiotemporal Control of Intracellular Membrane Trafficking by Rho GTPases

Members of the OSBP Homologue (Osh) Protein Family in S. cerevisiae Require Specific Lipids to Regulate Polarized Exocytosis

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