The Motility-Associated Proteins GAP-43, MARCKS, and CAP-23 Share Unique Targeting and Surface Activity-Inducing Properties

Wiederkehr, Andreas; Staple, Julie; Caroni, Pico

doi:10.1006/excr.1997.3709

Cited by 81 publications

(89 citation statements)

References 37 publications

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“…15 Despite its wide expression, the functions of BASP1 have only been characterized in neurons and podocytes while remaining poorly understood in other cell types. Available data suggest that BASP1 is a multifunctional protein that may behave as a transcription factor and may have lipid raft and cytoskeletal organizational properties 15,18,27 ; either of these properties could contribute to apoptosis. BASP1 regulates transcription by acting as a cosuppressor for WT1 in glomerular epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…[37][38][39] BASP1/cortical cytoskeleton-associated protein 23, growth-associated protein 43 (GAP43), and myristoylated alanine-rich C-kinase substrate (MARCKS) define a novel class of functionally related proteins (termed "GMC proteins") that share the ED domain and certain properties (e.g., acylation-mediated targeting to the cell membrane and association with the cortical cytoskeleton). 18 BASP1, GAP43 and MARCKS bind to and can regulate key actin binding proteins such as gelsolin and cofilin. 40,41 Although a role for BASP1 in apoptosis is novel, it has been suggested for other GMC proteins, although the molecular pathways are not well understood.…”

Section: Basic Research Wwwjasnorgmentioning

confidence: 99%

“…17 In addition, BASP1 promotes actin dynamics, including loss of stress fibers and bleb formation. 18 Additionally, BASP1 is present in the developing nephron structures of the embryonic kidney coinciding with the transcriptional regulator Wilm's tumor gene (WT1). In the adult kidney the main site of BASP1 expression is the podocyte, where it behaves as a transcriptional cosuppressor of WT1.…”

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confidence: 99%

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BASP1 Promotes Apoptosis in Diabetic Nephropathy

Sanchez-Niño¹,

Sanz

Lorz³

et al. 2010

Journal of the American Society of Nephrology

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Apoptosis contributes to the development of diabetic nephropathy (DN), but the mechanisms that lead to diabetes-induced cell death are not fully understood. Here, we combined a functional genomics screen for cDNAs that induce apoptosis in vitro with transcriptional profiling of renal biopsies from patients with DN. Twelve of the 138 full-length cDNAs that induced cell death in human embryonic kidney cells matched upregulated mRNA transcripts in tissue from human DN. Confirmatory screens identified induction of BASP1 in tubular cross sections of human DN tissue. In vitro, apoptosis-inducing conditions such as serum deprivation, high concentrations of glucose, and proinflammatory cytokines increased BASP1 mRNA and protein in human tubular epithelial cells. In normal cells, BASP1 localized to the cytoplasm, but in apoptotic cells, it colocalized with actin in the periphery. Overexpression of BASP1 induced cell death with features of apoptosis; conversely, small interfering RNA (siRNA)-mediated knockdown of BASP1 protected tubular cells from apoptosis. Supporting possible involvement of BASP1 in renal disease other than DN, we also observed significant upregulation of renal BASP1 in spontaneously hypertensive rats and a trend toward increased tubulointerstitial BASP1 mRNA in human hypertensive nephropathy. In summary, a combined functional genomics approach identified BASP1 as a proapoptotic factor in DN and possibly also in hypertensive nephropathy.

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Section: Discussionmentioning

confidence: 99%

Section: Basic Research Wwwjasnorgmentioning

confidence: 99%

mentioning

confidence: 99%

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BASP1 Promotes Apoptosis in Diabetic Nephropathy

Sanchez-Niño¹,

Sanz

Lorz³

et al. 2010

Journal of the American Society of Nephrology

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“…61 Furthermore, MLP (MARCKS-like protein) that was also found upregulated in cluster B is able to interact with tetraspanins and is a substrate for protein kinase C and may function as a regulator of cortical cytoskeleton dynamics in cell spreading and migration. 62 Additional evaluation of these candidate genes in clinical tissue specimens is required in order to establish their involvement in metastasis. A better understanding of the regulation of metastasis is necessary for the discovery of novel therapeutic targets and for better assessment of individual risk for tumor progression, especially in types of cancer such as pancreatic adenocarcinoma with extremely high occurrence of metastasis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of gene expression in cancer cell lines identifies candidate markers for pancreatic tumorigenesis and metastasis

Missiaglia

Blaveri

Terris

et al. 2004

Intl Journal of Cancer

139

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Pancreatic cancer is a highly aggressive type of malignancy and the prognosis for disease presenting typically at a late stage is extremely poor. A comprehensive understanding of its molecular genetics is required in order to develop new approaches to clinical management. To date, serial analysis of gene expression and more recently oligo/cDNA microarray technologies have been employed in order to identify genes involved in pancreatic neoplasia that can be developed as diagnostic markers and drug targets for this dismal disease. This study describes the expression profile obtained from 20 pancreatic cell lines using cDNA microarrays containing 9,932 human gene elements. Numerous genes were identified as being differentially expressed, some of which have been previously implicated in pancreatic adenocarcinoma (S100P, S100A4, prostate stem cell antigen, lipocalin 2, claudins 3 and 4, trefoil factors 1 and 2) as well as several novel genes. The differentially expressed genes identified are involved in a variety of cellular functions, including control of transcription, regulation of the cell cycle, proteolysis, cell adhesion and signaling. Validation of our array results was performed by exploring the SAGEmap database and by immunohistochemistry for a selection of 4 genes that have not previously been studied in pancreatic cancer: anterior gradient 2 homologue (Xenopus laevis), insulin-like growth factor binding protein 3 and 4 and Forkhead box J1. Immunostaining was performed using pancreas-specific tissue microarrays containing core biopsies from 305 clinical specimens. In addition, using statistical group comparison and hierarchical clustering, a selection of genes was identified that may be linked to the site of metastasis from which these cell lines were isolated.

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“…In this model GAP-43 is predicted to have minimal direct interactions with actin. GAP-43 was found to codistribute with MARCKS and CAP-23, suggesting that the three proteins are functionally related [99]. All three proteins have positively charged effector domains, and all three bind calmodulin, PI (4,5) P 2 , and actin, and are phosphorylated by protein kinase C within the effector domain [51,99].…”

Section: Gap-43 Mechanism Of Action: Interactions With Calmodulin Acmentioning

confidence: 99%

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

Denny

2006

203

166

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GAP-43 is an intracellular growth-associated protein that appears to assist neuronal pathfinding and branching during development and regeneration, and may contribute to presynaptic membrane changes in the adult, leading to the phenomena of neurotransmitter release, endocytosis and synaptic vesicle recycling, long-term potentiation, spatial memory formation, and learning. GAP-43 becomes bound via palmitoylation and the presence of three basic residues to membranes of the early secretory pathway. It is then sorted onto vesicles at the late secretory pathway for fast axonal transport to the growth cone or presynaptic plasma membrane. The palmitate chains do not serve as permanent membrane anchors for GAP-43, because at steady-state most of the GAP-43 in a cell is membrane-bound but is not palmitoylated. Filopodial extension and branching take place when GAP-43 is phosphorylated at Ser-41 by protein kinase C, and this occurs following neurotrophin binding and the activation of numerous small GTPases. GAP-43 has been proposed to cluster the acidic phospholipid phosphatidylinositol 4,5-bisphosphate in plasma membrane rafts. Following GAP-43 phosphorylation, this phospholipid is released to promote local actin filament-membrane attachment. The phosphorylation also releases GAP-43 from calmodulin. The released GAP-43 may then act as a lateral stabilizer of actin filaments. N-terminal fragments of GAP-43, containing 10-20 amino acids, will activate heterotrimeric G proteins, direct GAP-43 to the membrane and lipid rafts, and cause the formation of filopodia, possibly by causing a change in membrane tension. This review will focus on new information regarding GAP-43, including its binding to membranes and its incorporation into lipid rafts, its mechanism of action, and how it affects and is affected by extracellular agents.

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The Motility-Associated Proteins GAP-43, MARCKS, and CAP-23 Share Unique Targeting and Surface Activity-Inducing Properties

Cited by 81 publications

References 37 publications

BASP1 Promotes Apoptosis in Diabetic Nephropathy

BASP1 Promotes Apoptosis in Diabetic Nephropathy

Analysis of gene expression in cancer cell lines identifies candidate markers for pancreatic tumorigenesis and metastasis

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

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