Blood vessel epicardial substance

From Wikipedia, the free encyclopedia
Jump to: navigation, search

For the BVES stock exchange see Salvadoran Stock Exchange

BVES
Identifiers
Aliases BVES, HPOP1, POPDC1, LGMD2X, blood vessel epicardial substance
External IDs MGI: 1346013 HomoloGene: 48497 GeneCards: BVES
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001199563
NM_007073
NM_147147

NM_024285

RefSeq (protein)

NP_001186492
NP_009004
NP_671488

NP_077247.1
NP_077247

Location (UCSC) Chr 6: 105.1 – 105.14 Mb Chr 10: 45.34 – 45.37 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Blood vessel epicardial substance (BVES) also known as popeye domain-containing protein 1 (POPDC1) is a protein that in humans is encoded by the BVES gene.[3][4]

Bves is a highly conserved, transmembrane protein that is involved in cell adhesion, cell motility, and most recently has been shown to play a role in vesicular transport.[5][6][7][8] Bves is found in a wide variety of organisms (from flies to humans) and is a member of the evolutionarily conserved Popdc family of proteins. Although the precise molecular function of Bves is unknown, disruption of this protein results in developmental defects and impaired cellular processes fundamental to living organisms.[9][10][11]

Discovery[edit]

Bves was discovered simultaneously by two independent labs in 1999 (Bves was also named Popdc1 at the time of discovery; the current accepted convention is Bves).[4][12] Although initially isolated from cardiac tissue, it was later revealed that Bves is highly expressed in muscle, epithelial and brain tissue.[6] Most studies have focused on determining the function of Bves in epithelial tissue at the cellular level.

Gene family[edit]

Bves is the most studied member of the Popeye domain containing (Popdc) family of genes. The two other members of this family are Popdc2 and Popdc3. Popdc2 and Popdc3 are only found in higher vertebrates and share 50% of their DNA sequence, whereas Bves is only 25% homologous with the evolutionary younger Popdc family members. All three members of the Popdc family contain the highly conserved Popeye domain as the family was named for this specific protein motif.[5][6][7]

Structure[edit]

Bves is a three-pass transmembrane protein with a short extracellular N-terminus (~40aa) and a larger intracellular C-terminus (~250aa).[13] Within the C-terminus is the Popeye domain, which has been postulated to be important for Bves function. The Popeye domain shares no homology with any known protein motifs, and specific function of this domain is currently unknown, although it is highly conserved across species. Bves exists as a homodimer in vivo, and homodimerization has been shown to be important for function.[14]

Localization/expression[edit]

Bves is expressed in muscle, epithelial and brain tissue, and is thus found in many adult organs.[7] During development, Bves is detected in all three germ layers and later localizes to the aforementioned tissues.[15] Subcellular localization is present at the plasma membrane and is also seen in punctate, intracellular vesicles. Bves demonstrates dynamic localization, dependent upon cell-cell junction formation. Prior to cell-cell contact, Bves is localized mostly to intracellular vesicles, but as cells begin to form associations, Bves is also present at points of cell-cell contact.[9]

Interacting proteins[edit]

Bves interacts with GEFT, a protein that modulates Rho GTPases, Rac1 and Cdc42, which are important for cell motility through modulation of the actin cytoskeleton.[11] Bves also interacts with VAMP3, a SNARE protein important for vesicle fusion.[8] Additionally, Bves has been shown to interact with the tight junction protein, ZO1, although this interaction is most likely via a protein complex, as a direct physical interaction has never been demonstrated.[9]

Function[edit]

Disruption of Bves results in a wide range of cellular and developmental phenotypes. Grossly, cell motility and cell adhesion are impaired. Only recently have the molecular mechanisms underlying the function of Bves been uncovered.

Modulation of Rho GTPases[edit]

Bves has been shown to interact and co-localize with GEFT, a modulator of Rho GTPase signaling cascades. Disruption of Bves results in decreased cell speed and increased cell roundness, which are cell processes modulated by the Rho GTPases, Rac1 and Cdc42. Accordingly, Bves disruption results in decreased active Rac1 and Cdc42. Taken together, these data demonstrate that Bves modulates Rho GTPase signaling cascades through interaction with GEFT to affect cell movement and morphology.[11]

Regulation of vesicular transport[edit]

Bves has been shown to interact with VAMP3, a member of the SNARE complex that facilitates vesicle fusion. VAMP3 is important for recycling of integrins during cell migration and is also necessary for exocytosis of transferrin.[16][17][18][19][20] Upon Bves disruption, cell rounding is increased, a phenotype indicative of decreased adhesion and disruption of integrin function. Accordingly, Bves disruption results in impaired integrin recycling, phenocopying the result seen with inhibition of VAMP3. Similarly, disruption of either Bves results in impaired transferrin recycling again, mimicking the result seen with disruption of VAMP3. Thus, Bves is important for VAMP3-mediated vesicular transport underlying cell migration and transferrin recycling.[8]

Silencing in malignancy[edit]

Bves is silenced by promoter hypermethylation in malignancy. Bves is underexpressed in colon, lung, and breast cancer. In colon cancer this occurs very early during tumorigenesis, with Bves underexpression first noted in premalignant adenomas.

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Reese DE, Bader DM (Sep 1999). "Cloning and expression of hbves, a novel and highly conserved mRNA expressed in the developing and adult heart and skeletal muscle in the human". Mammalian Genome. 10 (9): 913–5. doi:10.1007/s003359901113. PMID 10441744. 
  4. ^ a b Andrée B, Hillemann T, Kessler-Icekson G, Schmitt-John T, Jockusch H, Arnold HH, Brand T (Jul 2000). "Isolation and characterization of the novel popeye gene family expressed in skeletal muscle and heart". Developmental Biology. 223 (2): 371–82. doi:10.1006/dbio.2000.9751. PMID 10882522. 
  5. ^ a b Brand T (2005). "The Popeye domain-containing gene family". Cell Biochemistry and Biophysics. 43 (1): 95–103. doi:10.1385/CBB:43:1:095. PMID 16043887. 
  6. ^ a b c Osler ME, Smith TK, Bader DM (Mar 2006). "Bves, a member of the Popeye domain-containing gene family". Developmental Dynamics. 235 (3): 586–93. doi:10.1002/dvdy.20688. PMC 2849751Freely accessible. PMID 16444674. 
  7. ^ a b c Hager HA, Bader DM (Jun 2009). "Bves: ten years after". Histology and Histopathology. 24 (6): 777–87. PMC 2853719Freely accessible. PMID 19337975. 
  8. ^ a b c Hager HA, Roberts RJ, Cross EE, Proux-Gillardeaux V, Bader DM (Feb 2010). "Identification of a novel Bves function: regulation of vesicular transport". The EMBO Journal. 29 (3): 532–45. doi:10.1038/emboj.2009.379. PMC 2830705Freely accessible. PMID 20057356. 
  9. ^ a b c Osler ME, Chang MS, Bader DM (Oct 2005). "Bves modulates epithelial integrity through an interaction at the tight junction". Journal of Cell Science. 118 (Pt 20): 4667–78. doi:10.1242/jcs.02588. PMID 16188940. 
  10. ^ Ripley AN, Osler ME, Wright CV, Bader D (Jan 2006). "Xbves is a regulator of epithelial movement during early Xenopus laevis development". Proceedings of the National Academy of Sciences of the United States of America. 103 (3): 614–9. doi:10.1073/pnas.0506095103. PMC 1334639Freely accessible. PMID 16407138. 
  11. ^ a b c Smith TK, Hager HA, Francis R, Kilkenny DM, Lo CW, Bader DM (Jun 2008). "Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity". Proceedings of the National Academy of Sciences of the United States of America. 105 (24): 8298–303. doi:10.1073/pnas.0802345105. PMC 2423412Freely accessible. PMID 18541910. 
  12. ^ Reese DE, Zavaljevski M, Streiff NL, Bader D (May 1999). "bves: A novel gene expressed during coronary blood vessel development". Developmental Biology. 209 (1): 159–71. doi:10.1006/dbio.1999.9246. PMID 10208750. 
  13. ^ Knight RF, Bader DM, Backstrom JR (Aug 2003). "Membrane topology of Bves/Pop1A, a cell adhesion molecule that displays dynamic changes in cellular distribution during development". The Journal of Biological Chemistry. 278 (35): 32872–9. doi:10.1074/jbc.M301961200. PMID 12815060. 
  14. ^ Kawaguchi M, Hager HA, Wada A, Koyama T, Chang MS, Bader DM (2008). "Identification of a novel intracellular interaction domain essential for Bves function". PLOS ONE. 3 (5): e2261. doi:10.1371/journal.pone.0002261. PMC 2373926Freely accessible. PMID 18493308.  open access publication – free to read
  15. ^ Osler ME, Bader DM (Mar 2004). "Bves expression during avian embryogenesis". Developmental Dynamics. 229 (3): 658–67. doi:10.1002/dvdy.10490. PMID 14991721. 
  16. ^ McMahon HT, Ushkaryov YA, Edelmann L, Link E, Binz T, Niemann H, Jahn R, Südhof TC (Jul 1993). "Cellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein". Nature. 364 (6435): 346–9. doi:10.1038/364346a0. PMID 8332193. 
  17. ^ Proux-Gillardeaux V, Gavard J, Irinopoulou T, Mège RM, Galli T (May 2005). "Tetanus neurotoxin-mediated cleavage of cellubrevin impairs epithelial cell migration and integrin-dependent cell adhesion". Proceedings of the National Academy of Sciences of the United States of America. 102 (18): 6362–7. doi:10.1073/pnas.0409613102. PMC 1088364Freely accessible. PMID 15851685. 
  18. ^ Skalski M, Coppolino MG (Oct 2005). "SNARE-mediated trafficking of alpha5beta1 integrin is required for spreading in CHO cells". Biochemical and Biophysical Research Communications. 335 (4): 1199–210. doi:10.1016/j.bbrc.2005.07.195. PMID 16112083. 
  19. ^ Tayeb MA, Skalski M, Cha MC, Kean MJ, Scaife M, Coppolino MG (Apr 2005). "Inhibition of SNARE-mediated membrane traffic impairs cell migration". Experimental Cell Research. 305 (1): 63–73. doi:10.1016/j.yexcr.2004.12.004. PMID 15777788. 
  20. ^ Luftman K, Hasan N, Day P, Hardee D, Hu C (Feb 2009). "Silencing of VAMP3 inhibits cell migration and integrin-mediated adhesion". Biochemical and Biophysical Research Communications. 380 (1): 65–70. doi:10.1016/j.bbrc.2009.01.036. PMC 2716655Freely accessible. PMID 19159614. 

External links[edit]