Mammalian Adenylyl Cyclase-associated Protein 1 (CAP1) Regulates Cofilin Function, the Actin Cytoskeleton, and Cell Adhesion

Zhang, Haitao; Ghai, Pooja; Wu, Huhehasi; Wang, Changhui; Field, Jeffrey; Zhou, Guowei

doi:10.1074/jbc.m113.484535

Cited by 82 publications

(116 citation statements)

References 64 publications

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“…[12][13][14]25 In contrast to the reduced motility in some cell types, CAP1 knockdown in HeLa cells, however, actually stimulated cell motility and invasion. 5 The CAP1-knockdown HeLa cells also had increased lamellipodia, which could explain the observed cell migration phenotype. Furthermore, CAP1-knockdown HeLa cells had significantly enhanced cell spreading and adhesion.…”

Section: Effects Of Cap1 Depletion On the Actin Cytoskeleton And Cellmentioning

confidence: 93%

“…While most data suggesting that CAP1 interacts with cofilin are from in vitro studies, there is some evidence that they interact in cells because depletion of mammalian CAP1 causes cofilin to accumulate into cytoplasmic aggregates 5,25 and remain dephosphorylated. 5 Aggregation is likely to prevent cofilin from functioning to facilitate actin filament dynamics.…”

Section: Cap1 As a Key Actin-regulatory Protein That Promotes Cofilinmentioning

confidence: 99%

“…In CAP1-depleted NIH3T3 fibroblasts, B16F1, and HeLa cells, common actin cytoskeletal (and morphological) alterations observed include enhanced actin stress fibers and enlarged cell size. 5,25 The enhanced stress fibers in the CAP1 knockdowns are likely to be caused by the reduced rate of the actin filament turnover and reduced G-actinsequestering. While stress fibers generate tension force needed to pull the trailing edge forward during cell movement, enhanced stress fibers is typically associated with reduced motility.…”

Section: Effects Of Cap1 Depletion On the Actin Cytoskeleton And Cellmentioning

confidence: 99%

“…Furthermore, CAP1-knockdown HeLa cells had significantly enhanced cell spreading and adhesion. 5 Cell adhesion, through integrin activation, plays an important role in cell migration as it provides traction force essential for cell migration. 30 Sufficient traction force will not be generated if there is too little adhesion for the cells to attach well; on the other hand, too much cell adhesion causes abnormally strong cell attachment, which will also hinder motility.…”

Section: Effects Of Cap1 Depletion On the Actin Cytoskeleton And Cellmentioning

confidence: 99%

“…1 In contrast, up to 50% of the total cytoplasmic actin in cells remains unpolymerized, despite being ~100-fold greater than the critical concentration. [2][3][4][5] It is most likely that the high concentrations of G-actin are maintained by actin-binding proteins, which sequester G-actin to prevent polymerization. 6 One G-actinsequestering protein is CAP (Cyclaseassociated protein), which is conserved in all eukaryotes, and has been studied for the past two decades.…”

Section: Introductionmentioning

confidence: 99%

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Mammalian CAP (Cyclase-associated protein) in the world of cell migration

Zhou

Zhang

Field

2013

Cell Adhesion & Migration

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Section: Effects Of Cap1 Depletion On the Actin Cytoskeleton And Cellmentioning

confidence: 93%

Section: Cap1 As a Key Actin-regulatory Protein That Promotes Cofilinmentioning

confidence: 99%

Section: Effects Of Cap1 Depletion On the Actin Cytoskeleton And Cellmentioning

confidence: 99%

Section: Effects Of Cap1 Depletion On the Actin Cytoskeleton And Cellmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mammalian CAP (Cyclase-associated protein) in the world of cell migration

Zhou

Zhang

Field

2013

Cell Adhesion & Migration

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High Cell Density Perfusion Culture has a Maintained Exoproteome and Metabolome

Zamani

Lundqvist

Zhang

et al. 2018

Biotechnology Journal

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The optimization of bioprocesses for biopharmaceutical manufacturing by Chinese hamster ovary (CHO) cells can be a challenging endeavor and, today, heavily relies on empirical methods treating the bioreactor process and the cells as black boxes. Multi-omics approaches have the potential to reveal otherwise unknown characteristics of these systems and identify culture parameters to more rationally optimize the cultivation process. Here, the authors have applied both metabolomic and proteomic profiling to a perfusion process, using CHO cells for antibody production, to explore how cell biology and reactor environment change as the cell density reaches ≥200 × 10 cells mL . The extracellular metabolic composition obtained in perfusion mode shows a markedly more stable profile in comparison to fed-batch, despite a far larger range of viable cell densities in perfusion. This stable profile is confirmed in the extracellular proteosome. Furthermore, the proteomics data shows an increase of structural proteins as cell density increases, which could be due to a higher shear stress and explain the decrease in cell diameter at very high cell densities. Both proteomic and metabolic results shows signs of oxidative stress and changes in glutathione metabolism at very high cell densities. The authors suggest the methodology presented herein to be a powerful tool for optimizing processes of recombinant protein production.

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Cyclase‐associated protein 1 is a key negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells

Yuan

Zhen

Zhang

et al. 2019

Cell Biochemistry & Function

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Adenylyl cyclase-associated protein (CAP) is a highly conserved protein. Previous reports have suggested that CAP1 may be a negative regulator of cellular proliferation, migration, and adhesion and the development of cell carcinomas. The molecular mechanism of CAP1 regulation of downstream pathways, as well as how CAP1 is regulated by environmental stimuli and upstream signalling, is not well understood. In this present study, we assessed the role of CAP1 in milk synthesis and proliferation of bovine mammary epithelial cells. Using gene overexpression and silencing methods, CAP1 was found to negatively regulate milk synthesis and proliferation of cells via the PI3K-mTOR/SREBP-1c/Cyclin D1 signalling pathway. Hormones, such as prolactin and oestrogen, and amino acids, such as methionine and leucine, stimulate MMP9 expression and trigger CAP1 degradation, and thus, abrogate its inhibition of synthesis of milk protein, fat, and lactose by and proliferation of bovine mammary epithelial cells.The results of our study help deepen our understanding of the regulatory mechanisms underlying milk synthesis and aid in characterizing the molecular mechanisms of CAP1.Previous reports have suggested that CAP1 is a negative regulator of cellular proliferation and anabolism, but the molecular mechanisms are largely unknown. In this present study, we identified CAP1 as a negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells. Our results will deepen our understanding of the regulatory mechanisms underlying milk synthesis and aid in exploring the molecular mechanisms of CAP1.

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Mammalian Adenylyl Cyclase-associated Protein 1 (CAP1) Regulates Cofilin Function, the Actin Cytoskeleton, and Cell Adhesion

Cited by 82 publications

References 64 publications

Mammalian CAP (Cyclase-associated protein) in the world of cell migration

Mammalian CAP (Cyclase-associated protein) in the world of cell migration

High Cell Density Perfusion Culture has a Maintained Exoproteome and Metabolome

Cyclase‐associated protein 1 is a key negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells

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