Differential regulation of cortactin and N-WASP-mediated actin polymerization by missing in metastasis (MIM) protein

Lin, Jinxiu; Liu, Jiali; Wang, Ying; Zhu, Jianwei; Zhou, Kang; Smith, Nicole; Zhan, Xi

doi:10.1038/sj.onc.1208412

Cited by 90 publications

(135 citation statements)

References 28 publications

(26 reference statements)

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“…Physical interaction between MTSS1 and Rac has been documented earlier; to the best of our knowledge, however, RhoA-MTSS1 engagement has previously not been reported. While these data are supported by observations from other cell lines where ectopic expression of MTSS1 or its I-BAR domain results in reduction of stress fibers 35 , a hallmark phenotype for RhoA inactivation 62 , they do not exclude additional indirect Rac and RhoA regulation through MTSS1 by affecting the geometry or lipid distribution of the leading edge plasma membrane through its I-BAR domain 26 or by altering the structure of the actin cytoskeleton through its interactions with cortactin or Daam1 formin 63,64 . It is also interesting to note that in contrast to earlier reports about MTSS1 to activate Rac 37 , but consistent with Rac's dispensability for I-BAR-induced filopodia formation 34 , we observed a reduction of Rac activity in HMEL cells upon MTSS1 expression.…”

Section: Discussionsupporting

confidence: 63%

“…In addition to overexpression, the interplay of MTSS1 with other components of the cytoskeletal machinery to confer cell mobility is subject to a high degree of regulation. This includes (i) the extent of alternative splicing leading to the expression of MTSS1-isoforms composed of different functional domains 60 , (ii) the degree of expression of, substitution by and/or competition with other BAR domain protein family members and lipid-binding proteins 65 that interfere with binding of MTSS1 to its substrates such as Cortactin 61,63 , (iii) the level of competition with other actin-binding adaptor molecules such as N-WASP for binding to active actin monomers 63 and (iv) presumably the expression of MTSS1's substrates in different cellular contexts.…”

Section: Discussionmentioning

confidence: 99%

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MTSS1 is a metastasis driver in a subset of human melanomas

et al. 2014

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In cancers with a highly altered genome, distinct genetic alterations drive subsets rather than the majority of individual tumours. Here we use a sequential search across human tumour samples for transcript outlier data points with associated gene copy number variations that correlate with patient's survival to identify genes with pro-invasive functionality. Employing loss and gain of function approaches in vitro and in vivo, we show that one such gene, MTSS1, promotes the ability of melanocytic cells to metastasize and engages actin dynamics via Rho-GTPases and cofilin in this process. Indeed, high MTSS1 expression defines a subgroup of primary melanomas with unfavourable prognosis. These data underscore the biological, clinical and potential therapeutic implications of molecular subsets within genetically complex cancers.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

MTSS1 is a metastasis driver in a subset of human melanomas

et al. 2014

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“…has been implicated in cellular migration (Bompard et al, 2005;Lin et al, 2005). Array analysis indicated that mtss1 mRNA expression was down-regulated in L7En-2 animals around P7, but not in newborns or in adults (Table 2).…”

Section: Array Hybridization and Verificationmentioning

confidence: 99%

“…Spectrin beta2, identified here as down-regulated in En-2 overexpressing Purkinje cells, forms protein scaffolds beneath the plasma membrane and restricts transport to specialized membrane domains (Dubreuil, 2006). Similarly, Mtss1 regulates Cortactin and N-WASP-mediated actin polymerization (Lin et al, 2005) and is localized to dendritic spines (Mattila et al, 2007). In addition, Actinin 2 up-regulated in L7En-2 cerebella interacts with actin filaments and postsynaptic density proteins, and recruits glutamate receptors to dendritic spines (Wyszynski et al, 1998).…”

Section: Intracellular Transport and Sorting Of Vesicles Are Targetedmentioning

confidence: 99%

Engrailed-2 regulates genes related to vesicle formation and transport in cerebellar Purkinje cells

Holst

Maercker

Pintea

et al. 2008

Molecular and Cellular Neuroscience

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“…In skin epithelial cells, MTSS1 was found to associate with Gli, a major signaling target of the Sonic hedgehog pathway, and activate the transcriptional activity of Gli within cells (18). We have recently observed that Mtss1, a murine protein sharing 96.3% identity with MTSS1, binds to cortactin through the proline-rich domain and promotes the cortactin-mediated actin assembly (19). On the other hand, Mtss1 inhibits the actin polymerization mediated by a spontaneous process or by neuronal (N)-WASP-activated Arp2/3 complex (19).…”

mentioning

confidence: 99%

Tyrosine Phosphorylation of Missing in Metastasis Protein Is Implicated in Platelet-derived Growth Factor-mediated Cell Shape Changes

Wang

Zhou

Zeng

et al. 2007

Journal of Biological Chemistry

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Missing in metastasis gene, or MTSS1, encodes an intracellular protein that is implicated in actin cytoskeleton reorganization and often down-regulated in certain types of tumor cells. In response to platelet-derived growth factor (PDGF), green fluorescent protein (GFP)-tagged murine Mtss1 (Mtss1-GFP) underwent redistribution from the cytoplasm to dorsal membrane ruffles along with phosphorylation at tyrosine residues in a time-dependent manner. Tyrosine phosphorylation of Mtss1-GFP was also elevated in cells where an oncogenic Src was activated but severely impaired in Src knock-out cells or cells treated with Src kinase inhibitor PP2. Mutagenesis analysis has revealed that phosphorylation occurs at multiple sites, including tyrosine residues Tyr-397 and Tyr-398. Mutation at both Tyr-397 and Tyr-398 abolished the PDGF-mediated tyrosine phosphorylation. Furthermore, recombinant Mtss1 protein was phosphorylated by recombinant Src in a manner dependent on Tyr-397 and Tyr-398. Efficient tyrosine phosphorylation of Mtss1 in response to PDGF also involves a coiled-coil domain, which is essential for a proper distribution to the cell leading edge and dorsal ruffles. Interestingly, overexpression of wild type Mtss1-GFP promoted the PDGF-induced dorsal ruffling, whereas overexpression of a mutant deficient in phosphorylation at Tyr-397 and Tyr-398 or a mutant with deletion of the coiled-coil domain impaired the formation of dorsal ruffles. These data indicate that Mtss1 represents a novel signaling pathway from PDGF receptor to the actin cytoskeleton via Srcrelated kinases.Growth factor-mediated cytoskeletal reorganization plays a pivotal role in cell shape changes, locomotion, endocytosis, and homeostasis. The signal transduction elicited by ligand-occupied receptors initially involves activation of several small guanosine triphosphatase proteins, including Rac, Cdc42, and Rho (1). Activated Cdc42 or Rac binds either directly or indirectly to Wiskott-Aldrich Syndrome protein (WASP) 2 or WASP family verprolin homologous protein (WAVE/Scar), resulting in recruitment of these proteins to the plasma membrane wherein they subsequently activate Arp2/3 complex, an actin nucleation factor for the branched actin filaments that constitute lamellipodia and membrane ruffles (2). On the other hand, activation of Rho promotes the assembly of nonbranched actin filaments through the function of the Formin family proteins, which may be responsible for the formation of stress fibers or actin cables (3). In addition to these relatively well established signaling factors, there are a few actin-associated proteins the role of which in the cytoskeletal reorganization remains to be defined. One of these proteins is MIM, which stands for missing in metastasis, or MTSS1 as recently recommended by Human Genome Organization Gene Nomenclature Committee. Previous studies have reported the existence of multiple MIM splicing transcripts, including MIM-A, the prototype of MIM that encodes only 356 amino acids; MIM-B, which encodes a protein product o...

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Differential regulation of cortactin and N-WASP-mediated actin polymerization by missing in metastasis (MIM) protein

Cited by 90 publications

References 28 publications

MTSS1 is a metastasis driver in a subset of human melanomas

MTSS1 is a metastasis driver in a subset of human melanomas

Engrailed-2 regulates genes related to vesicle formation and transport in cerebellar Purkinje cells

Tyrosine Phosphorylation of Missing in Metastasis Protein Is Implicated in Platelet-derived Growth Factor-mediated Cell Shape Changes

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