Widely Conserved Signaling Pathways in the Establishment of Cell Polarity

McCaffrey, Luke; Macara, Ian G.

doi:10.1101/cshperspect.a001370

Cited by 95 publications

(88 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, AfsK is involved in a stress response when cell wall synthesis is arrested; under such conditions, AfsK is strongly activated and causes profound reconfiguration of DivIVA localization, apical growth, and hyphal branching. This discovery represents an intriguing prokaryotic parallel to the widespread and broadly conserved roles of STKs in controlling cell polarity in eukaryotes (1,2), and particularly to the control of polar growth by kinases targeting polarisome components in fungi (references in ref. 13).…”

Section: Discussionmentioning

confidence: 99%

“…It typically involves the initial deposition of a landmark protein at a cellular locus, followed by reinforcement of the polarization mark by assembly of larger multiprotein complexes. In eukaryotes, these complexes include broadly conserved proteins involved in the reorganization and polarization of the cytoskeleton and other cellular constituents (1,2). Among the most pronounced cases of cell polarity are those in which growth or extension of the cell is targeted to a specific subcellular site, resulting in polar or apical growth.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces

Hempel

Cantlay

Molle

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

108

155

View full text Add to dashboard Cite

In cells that exhibit apical growth, mechanisms that regulate cell polarity are crucial for determination of cellular shape and for the adaptation of growth to intrinsic and extrinsic cues. Broadly conserved pathways control cell polarity in eukaryotes, but less is known about polarly growing prokaryotes. An evolutionarily ancient form of apical growth is found in the filamentous bacteria Streptomyces, and is directed by a polarisome-like complex involving the essential protein DivIVA. We report here that this bacterial polarization machinery is regulated by a eukaryotic-type Ser/Thr protein kinase, AfsK, which localizes to hyphal tips and phosphorylates DivIVA. During normal growth, AfsK regulates hyphal branching by modulating branch-site selection and some aspect of the underlying polarisome-splitting mechanism that controls branching of Streptomyces hyphae. Further, AfsK is activated by signals generated by the arrest of cell wall synthesis and directly communicates this to the polarisome by hyperphosphorylating DivIVA. Induction of high levels of DivIVA phosphorylation by using a constitutively active mutant AfsK causes disassembly of apical polarisomes, followed by establishment of multiple hyphal branches elsewhere in the cell, revealing a profound impact of this kinase on growth polarity. The function of AfsK is reminiscent of the phoshorylation of polarity proteins and polarisome components by Ser/Thr protein kinases in eukaryotes.hyphal growth | protein phosphorylation | peptidoglycan | cytoskeleton | tip extension

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces

Hempel

Cantlay

Molle

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

108

155

View full text Add to dashboard Cite

show abstract

“…Proper localization of polarity determinants, directed vesicle traffic, and regulated cytoskeletal dynamics are required for polarization in many cell types, including neurons and neural progenitors. Small GTPases coordinate these events to establish cell polarity in response to intra-and extracellular cues (Mellman and Nelson, 2008;McCaffrey and Macara, 2009;Hall and Lalli, 2010). Among these, the Ras-like GTPase Ral, of which there are two isoforms, RalA and RalB, has emerged as an important polarity regulator in a variety of contexts, including basolateral membrane trafficking and tight junction formation in epithelial cells (Shipitsin and Feig, 2004;Hazelett et al, 2011), polarized migration of fibroblasts and cancer cells (Rossé et al, 2006;Spiczka and Yeaman, 2008) and tumorigenesis (Camonis and White, 2005;Lim et al, 2005;Oxford et al, 2005;Bodemann and White, 2008;Hazelett and Yeaman, 2012).…”

Section: Introductionmentioning

confidence: 99%

RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal development

Das

Gajendra

Falenta

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

Cell polarization is essential for neuronal development in both the embryonic and postnatal brain. Here, using primary cultures, in vivo postnatal electroporation and conditional genetic ablation, we show that the Ras-like small GTPase RalA and its effector, the exocyst, regulate the morphology and polarized migration of neural progenitors derived from the subventricular zone, a major neurogenic niche in the postnatal brain. Active RalA promotes the direct binding between the exocyst subunit Exo84 and the PDZ domain of Par6 through a non-canonical PDZ-binding motif. Blocking the Exo84-Par6 interaction impairs polarization in postnatal neural progenitors and cultured embryonic neurons. Our results provide the first in vivo characterization of RalA function in the mammalian brain and highlight a novel molecular mechanism for cell polarization. Given that the exocyst and the Par complex are conserved in many tissues, the functional significance of their interaction and its regulation by RalA are likely to be important in a wide range of polarization events.

show abstract

“…A basic feature of cell polarity is the asymmetric organization of the plasma membrane (see McCaffrey and Macara 2009;Nelson 2009). This is mostly achieved through membrane trafficking along cytoskeleton tracks under the control of signaling molecules.…”

mentioning

confidence: 99%

“…regulate membrane trafficking during cell polarization (see McCaffrey and Macara 2009;Slaughter et al 2009). Reversely, vesicular trafficking is required for the polarized deposition and accrual of these regulators.…”

mentioning

confidence: 99%

Membrane Organization and Dynamics in Cell Polarity

Orlando¹,

Guo²

2009

Cold Spring Harbor Perspectives in Biology

View full text Add to dashboard Cite

The establishment and maintenance of cell polarity is important to a wide range of biological processes ranging from chemotaxis to embryogenesis. An essential feature of cell polarity is the asymmetric organization of proteins and lipids in the plasma membrane. In this article, we discuss how polarity regulators such as small GTP-binding proteins and phospholipids spatially and kinetically control vesicular trafficking and membrane organization. Conversely, we discuss how membrane trafficking contributes to cell polarization through delivery of polarity determinants and regulators to the plasma membrane.

show abstract

Widely Conserved Signaling Pathways in the Establishment of Cell Polarity

Cited by 95 publications

References 122 publications

The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces

The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces

RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal development

Membrane Organization and Dynamics in Cell Polarity

Contact Info

Product

Resources

About