PakB binds to the SH3 domain of<i>Dictyostelium</i>Abp1 and regulates its effects on cell polarity and early development

Yang, Yidai; Crawley, Scott W.; Li, Zhihao; Furmaniak-Kazmierczak, Emilia; Côté, Graham P.

doi:10.1091/mbc.e12-12-0883

Cited by 4 publications

(5 citation statements)

References 40 publications

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“…This uncharacterised protein contains an ADF/cofilin-like domain, suggesting a possible role in F-actin depolymerisation, which would be supported by its translocation kinetics. Further examples of microscopy based validation of the SILAC dynamics are shown for three known regulators of the cytoskeletal dynamics – PakB 40, 41 , KxcB 14 and RapGAP1 42, 43 (Fig. 5).…”

Section: Resultsmentioning

confidence: 96%

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

2014

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Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterise the rapid chemoattractant induced dynamic changes in the actin-myosin cytoskeleton and regulatory elements on a proteome wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role.

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Section: Resultsmentioning

confidence: 96%

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

2014

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“…The consequence of such distinction is not clear in Dictyostelium to humans who also have two PAK groups ( Arasada et al, 2006 ). The class I PAKs in Dictyostelium functionally established to be involved in cell polarity, actin-myosin assemble and phagocytosis ( Lee et al, 2004 ; Yang et al, 2013 ; Garcia et al, 2014 ; Phillips and Gomer, 2014 ). The six PAK isoforms share high sequence identity ∼50–70% in the catalytic kinase domain and PBD regions, while the rarely display any homology outside these regions.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, constitutively active PAKb mutant increases the rate of myosin I dependent processes such as pinocytosis/phagocytosis and disrupts cytokinesis. The constitutively active and C-terminal truncated active PAKb shows localization at rear-end of the migrating cell and cleavage-furrow during cell division ( Yang et al, 2013 ). The notable fact here is the opposite localization of PAKa and PAKb in migrating cells, one at the rear end and the other at the posterior end, respectively, suggests that the two proteins do not have an overlapping function.…”

Section: Resultsmentioning

confidence: 99%

Cdc42/Rac Interactive Binding Containing Effector Proteins in Unicellular Protozoans With Reference to Human Host: Locks of the Rho Signaling

2022

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Small GTPases are the key to actin cytoskeleton signaling, which opens the lock of effector proteins to forward the signal downstream in several cellular pathways. Actin cytoskeleton assembly is associated with cell polarity, adhesion, movement and other functions in eukaryotic cells. Rho proteins, specifically Cdc42 and Rac, are the primary regulators of actin cytoskeleton dynamics in higher and lower eukaryotes. Effector proteins, present in an inactive state gets activated after binding to the GTP bound Cdc42/Rac to relay a signal downstream. Cdc42/Rac interactive binding (CRIB) motif is an essential conserved sequence found in effector proteins to interact with Cdc42 or Rac. A diverse range of Cdc42/Rac and their effector proteins have evolved from lower to higher eukaryotes. The present study has identified and further classified CRIB containing effector proteins in lower eukaryotes, focusing on parasitic protozoans causing neglected tropical diseases and taking human proteins as a reference point to the highest evolved organism in the evolutionary trait. Lower eukaryotes’ CRIB containing proteins fall into conventional effector molecules, PAKs (p21 activated kinase), Wiskoit-Aldrich Syndrome proteins family, and some have unique domain combinations unlike any known proteins. We also highlight the correlation between the effector protein isoforms and their selective specificity for Cdc42 or Rac proteins during evolution. Here, we report CRIB containing effector proteins; ten in Dictyostelium and Entamoeba, fourteen in Acanthamoeba, one in Trypanosoma and Giardia. CRIB containing effector proteins that have been studied so far in humans are potential candidates for drug targets in cancer, neurological disorders, and others. Conventional CRIB containing proteins from protozoan parasites remain largely elusive and our data provides their identification and classification for further in-depth functional validations. The tropical diseases caused by protozoan parasites lack combinatorial drug targets as effective paradigms. Targeting signaling mechanisms operative in these pathogens can provide greater molecules in combatting their infections.

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“…PAKb was first purified as a myosin I heavy chain kinase (MIHCK) responsible for myosin ID (MyoD) activation [ 207 ]. Furthermore, Y2H, pull-down, and coimmunoprecipitation assays showed that, besides MyoD, PAKb binds MyoK and the actin-binding protein 1 (Abp1) [ 207 , 208 , 209 ]. PAKb increases the motor activity of MyoK and MyoD by phosphorylating their TED sites [ 207 , 208 ].…”

Section: Comparative Analysis Of the Rho Signalling In Dictyostelium And Mammalian Cellsmentioning

confidence: 99%

“…Interestingly, however, no specific significant defects in any of the myosin I-dependent processes could be detected in cells lacking PAKb, but they have a mild chemotaxis defect, suffer from the loss of polarity, and produce superfluous lateral pseudopodia [ 81 , 83 ]. PAKb binds to actin filaments by its actin filament-binding module at the N-terminal part of the protein, and it was suggested that a PAKb-Abp1 complex has a role in the cross linking of actin filaments [ 209 ]. A Y2H assay showed that the PAKb PBD binds the active Rac1A/B/C, F1, B, C, and GTPase domain of RacA [ 81 ] Interestingly, human Cdc42 and Rac1, but not RhoA, also interact with PAKb and stimulate its activity, indicating a conserved regulatory mechanism [ 210 ].…”

Section: Comparative Analysis Of the Rho Signalling In Dictyostelium And Mammalian Cellsmentioning

confidence: 99%

Regulation of the Actin Cytoskeleton via Rho GTPase Signalling in Dictyostelium and Mammalian Cells: A Parallel Slalom

Filić

Mijanović

Putar

et al. 2021

Cells

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Both Dictyostelium amoebae and mammalian cells are endowed with an elaborate actin cytoskeleton that enables them to perform a multitude of tasks essential for survival. Although these organisms diverged more than a billion years ago, their cells share the capability of chemotactic migration, large-scale endocytosis, binary division effected by actomyosin contraction, and various types of adhesions to other cells and to the extracellular environment. The composition and dynamics of the transient actin-based structures that are engaged in these processes are also astonishingly similar in these evolutionary distant organisms. The question arises whether this remarkable resemblance in the cellular motility hardware is accompanied by a similar correspondence in matching software, the signalling networks that govern the assembly of the actin cytoskeleton. Small GTPases from the Rho family play pivotal roles in the control of the actin cytoskeleton dynamics. Indicatively, Dictyostelium matches mammals in the number of these proteins. We give an overview of the Rho signalling pathways that regulate the actin dynamics in Dictyostelium and compare them with similar signalling networks in mammals. We also provide a phylogeny of Rho GTPases in Amoebozoa, which shows a variability of the Rho inventories across different clades found also in Metazoa.

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PakB binds to the SH3 domain ofDictyosteliumAbp1 and regulates its effects on cell polarity and early development

Cited by 4 publications

References 40 publications

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

Cdc42/Rac Interactive Binding Containing Effector Proteins in Unicellular Protozoans With Reference to Human Host: Locks of the Rho Signaling

Regulation of the Actin Cytoskeleton via Rho GTPase Signalling in Dictyostelium and Mammalian Cells: A Parallel Slalom

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