Opposite Surfaces of the Cdc15 F-BAR Domain Create a Membrane Platform That Coordinates Cytoskeletal and Signaling Components for Cytokinesis

Snider, Chloe E.; Chandra, Mintu; McDonald, Nathan A.; Willet, Alaina H.; Collier, Scott E.; Ohi, Melanie D.; Jackson, Lauren P.; Gould, Kathleen L.

doi:10.1016/j.celrep.2020.108526

Cited by 14 publications

(37 citation statements)

References 69 publications

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“…We found that Pxl1 phosphorylation reduces its ability to bind the F-BAR domain of Cdc15 in vitro, and because Pxl1-Cdc15 F-BAR domain interaction is the major mechanism of Pxl1 CR recruitment (Snider et al, 2020), our results provide a mechanistic explanation for the phosphorylation-mediated change we observe in Pxl1 localization in vivo. It also seems possible however that phosphorylation regulates Pxl1 protein levels given that we observed a ~two-fold increase in the abundance of Pxl1(9A) using tags for Pxl1 detection.…”

Section: Discussionsupporting

confidence: 56%

“…The N-terminus of Pxl1 is the site of Cdk1 phosphorylation and contains CR targeting information (Pinar et al, 2008). Pxl1 interacts directly with the F-BAR protein Cdc15 (Roberts-Galbraith et al, 2009;Bhattacharjee et al, 2020;Snider et al, 2020).…”

Section: Cdk1-mediated Phosphorylation Inhibits Pxl1 Binding To Cdc15's N-terminus But Not Its C-terminusmentioning

confidence: 99%

“…Because Cdk1 phosphorylation of the formin Cdc12 inhibits its interaction with Cdc15 (Willet et al, 2018), we tested whether Cdk1 phosphorylation inhibits Pxl1 binding to Cdc15 similarly. However, unlike Cdc12 (Willet et al, 2015a), Cdc15 has two known binding sites for Pxl1: one in the N-terminal F-BAR domain (Snider et al, 2020) and one comprised of the C-terminal intrinsically disordered region and SH3 domain (Cdc15C) (Bhattacharjee et al, 2020). We tested whether either of these Pxl1-Cdc15 interactions was modulated by Pxl1 phosphostate using sequential in vitro phosphorylation and binding assays.…”

Section: Cdk1-mediated Phosphorylation Inhibits Pxl1 Binding To Cdc15's N-terminus But Not Its C-terminusmentioning

confidence: 99%

“…The CR component Pxl1 arrives at the CR during its maturation (Ren et al, 2015). Pxl1 binds the F-BAR domain of the CR scaffold Cdc15, and this interaction is critical for Pxl1 CR localization (Snider et al, 2020). Pxl1 also binds a another site on Cdc15 that includes the SH3 domain and part of the intrinsically disordered region (Roberts-Galbraith et al, 2009;Bhattacharjee et al, 2020), and Cdc15's SH3 domain is important for Pxl1 assembly into the CR throughout cytokinesis (Cortes et al, 2015;Martin-Garcia et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, in pxl1∆ cells the phosphatase calcineurin (CN) is not recruited to the CR (Martin-Garcia et al, 2018). Indeed, mutating the Pxl1 binding site on the Cdc15 F-BAR dramatically reduces both Pxl1 and CN localization to the CR, leading to defects in CR nanoscale architecture and constriction (Snider et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Cdk1 phosphorylation of fission yeast paxillin inhibits its cytokinetic ring localization

Mangione

Chen

Gould

2021

MBoC

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Divisions of the genetic material and cytoplasm are coordinated spatially and temporally to ensure genome integrity. This coordination is mediated in part by the major cell cycle regulator cyclin-dependent kinase (Cdk1). Cdk1 activity peaks during mitosis, but during mitotic exit/cytokinesis Cdk1 activity is reduced, and phosphorylation of its substrates is reversed by various phosphatases including Cdc14, PP1, PP2A and PP2B. Cdk1 is known to phosphorylate several components of the actin- and myosin-based cytokinetic ring (CR) that mediates division of yeast and animal cells. Here we show that Cdk1 also phosphorylates the Schizosaccharomyces pombe CR-component paxillin Pxl1. We determined that both the Cdc14 phosphatase Clp1 and the PP1 phosphatase Dis2 contribute to Pxl1 dephosphorylation at mitotic exit, but PP2B/calcineurin does not. Preventing Pxl1 phosphorylation by Cdk1 results in increased Pxl1 levels, precocious Pxl1 recruitment to the division site, and increases the duration of CR constriction. In vitro, Cdk1-mediated phosphorylation of Pxl1 inhibits its interaction with the F-BAR domain of the cytokinetic scaffold Cdc15, thereby disrupting a major mechanism of Pxl1 recruitment. Thus, Pxl1 is a novel substrate through which S. pombe Cdk1 and opposing phosphatases coordinate mitosis and cytokinesis.

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Section: Discussionsupporting

confidence: 56%

Section: Cdk1-mediated Phosphorylation Inhibits Pxl1 Binding To Cdc15's N-terminus But Not Its C-terminusmentioning

confidence: 99%

Section: Cdk1-mediated Phosphorylation Inhibits Pxl1 Binding To Cdc15's N-terminus But Not Its C-terminusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cdk1 phosphorylation of fission yeast paxillin inhibits its cytokinetic ring localization

Mangione

Chen

Gould

2021

MBoC

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Role of Bin‐Amphiphysin‐Rvs (BAR) domain proteins in mediating neuronal signaling and disease

Mallik

Bhat

Kumar

2022

Synapse

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Several proteins contain signaling domains that can regulate the cell membrane dynamics as well as the underlying cytoskeleton. Among these, Bin-Amphiphysin-Rvs (BAR) domain-containing proteins, with their membrane deforming properties, have emerged as the key players in regulating neuronal morphology and inducing neuronal signaling that can modulate synaptic architecture. While the biochemical and structural basis of membrane deformation by the BAR-domain proteins has been extensively studied, the in vivo contexts in which these proteins function remain to be elucidated. Despite the discovery of BAR-domain proteins over 25 years ago, most of the studies have primarily focused on understanding the structural and biochemical properties and cell biological processes regulated by these proteins. Understanding the functional requirements of these proteins at the level of multicellular organisms and the way these proteins regulate biological processes remains a topic of intensive study.In this review, we discuss the functional roles of BAR-domain proteins in the context of membrane dynamics and cellular signaling. We highlight recent developments describing the functional role of these proteins in neuronal morphogenesis, synaptic function, and disease.

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PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders

Manso

Marcos

Ruiz-Martín

et al. 2022

Cell. Mol. Life Sci.

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Mutations in the adaptor protein PSTPIP1 cause a spectrum of autoinflammatory diseases, including PAPA and PAMI; however, the mechanism underlying these diseases remains unknown. Most of these mutations lie in PSTPIP1 F-BAR domain, which binds to LYP, a protein tyrosine phosphatase associated with arthritis and lupus. To shed light on the mechanism by which these mutations generate autoinflammatory disorders, we solved the structure of the F-BAR domain of PSTPIP1 alone and bound to the C-terminal homology segment of LYP, revealing a novel mechanism of recognition of Pro-rich motifs by proteins in which a single LYP molecule binds to the PSTPIP1 F-BAR dimer. The residues R228, D246, E250, and E257 of PSTPIP1 that are mutated in immunological diseases directly interact with LYP. These findings link the disruption of the PSTPIP1/LYP interaction to these diseases, and support a critical role for LYP phosphatase in their pathogenesis.

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Opposite Surfaces of the Cdc15 F-BAR Domain Create a Membrane Platform That Coordinates Cytoskeletal and Signaling Components for Cytokinesis

Cited by 14 publications

References 69 publications

Cdk1 phosphorylation of fission yeast paxillin inhibits its cytokinetic ring localization

Cdk1 phosphorylation of fission yeast paxillin inhibits its cytokinetic ring localization

Role of Bin‐Amphiphysin‐Rvs (BAR) domain proteins in mediating neuronal signaling and disease

PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders

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