Jean Vance

Last updated

Professor

Jean E. Vance

Ph.D., F.R.S.C.
Jean.vance.jpg
Jean Vance in 2017
Born
Glasgow, Scotland
CitizenshipBritish and Canadian
PartnerDennis E. Vance
Awards Fellow of the Royal Society of Canada
Wilhelm Bernhard International Lifetime Achievement Prize, EMBO (2018)
Scientific career
Institutions University of Alberta
University of British Columbia
University of California, San Diego
University of Pittsburgh
Doctoral advisor Ronald Bentley, University of Pittsburgh

Jean Vance is a British-Canadian biochemist. She is known for her pioneering [1] [2] work on subcellular organelles and for her discovery of a connection between the endoplasmic reticulum and the mitochondrial membrane. [3] She is a Professor of Medicine at the University of Alberta, Canada and a Fellow of the Royal Society of Canada.

Contents

Education

Vance earned her BSc in Chemistry from Bedford College, London, UK in 1964 and her Ph.D. from the University of Pittsburgh, USA in 1969, where she worked with Ronald Bentley. [4] She performed postdoctoral work at the University of Pittsburgh and the University of California, San Diego.

Career

After working at the University of British Columbia as a Lecturer, Vance joined the University of Alberta in 1987. [4] She began to study the synthesis of the lipids that make up the subcellular membranes that divide the cell into compartments. [5] At the time, the site(s) of synthesis of lipids and the mechanisms by which they were moved around the cell were mysterious. [1] Working with a preparation of mitochondria, she made the surprising [1] observation that rapid lipid synthesis occurred in a crude preparation containing additional membranes, but not in a highly purified mitochondrial fraction. [6] This led her to hypothesize that a specialized membrane compartment, which she called Fraction X, might be responsible for the transfer of lipids from the endoplasmic reticulum to mitochondria. [6] Although this idea was initially greeted with skepticism, [1] Vance was able to reconstitute the transfer of newly made lipids to mitochondria in a cell-free system. [7] She purified "Fraction X", renaming it the mitochondria-associated membrane (MAM) fraction, and showed that it contained highly active enzymes able to synthesize a variety of membrane components. [8] She proposed that the MAM might function as a "membrane bridge" between the endoplasmic reticulum and the mitochondria. [9] Although Vance's work was ahead of its time, [10] it was rediscovered in the late 2000s when other researchers began to identify specific proteins, called tethers, that form the contact points between organelles. [1] [11] The mitochondria-endoplasmic reticulum bridge Vance originally identified is now named the endoplasmic reticulum membrane protein complex and has been shown to be important in the function, positioning and inheritance of mitochondria. [12] [13] Impaired contact between the endoplasmic reticulum and mitochondria has been suggested to underlie the pathology of several neurodegenerative diseases, including Alzheimer's disease. [14] [15] The newly appreciated importance of contacts among different subcellular organelles led in 2018 to the founding of a journal devoted to the area, Contact, published by SAGE Publishing. [2]

Vance has also worked on the transport of lipids and cholesterol to growing neurons. [16] She discovered defects in cholesterol transport in neurons lacking the protein associated with Niemann–Pick disease type C, NPC1, [17] and found that these defects can be addressed by treatment with cyclodextrin. [18] She observed that growing neurons in vitro take up and use components from low-density lipoprotein and very low-density lipoprotein particles, [16] [19] and identified a role for lipoproteins provided by glial cells in stimulating nerve cell growth [20] and protecting neurons from apoptosis. [21]

In 2018 she was awarded the Wilhelm Bernhard International Lifetime Achievement Prize by the European Molecular Biology Organization. [2] [10]

Together with her husband and collaborator Dennis E. Vance, she co-edited the advanced textbook "Biochemistry of lipids, lipoproteins and membranes" [22] from 1985 until the 5th edition in 2008. [4]

Vance and her husband both elected to enrol in the University of Alberta's Transitional Retirement Program in 2017, planning to wind down their research over a three-year period. [23] Their son, Russell Vance, is an investigator of the Howard Hughes Medical Institute and a faculty member at the University of California, Berkeley. [24]

Related Research Articles

<span class="mw-page-title-main">Endoplasmic reticulum</span> Cell organelle that synthesizes, folds and processes proteins

The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae, and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa.

<span class="mw-page-title-main">Mediated transport</span> Transportation of substances via membrane

Mediated transport refers to transport mediated by a membrane transport protein. Substances in the human body may be hydrophobic, electrophilic, contain a positively or negatively charge, or have another property. As such there are times when those substances may not be able to pass over the cell membrane using protein-independent movement. The cell membrane is imbedded with many membrane transport proteins that allow such molecules to travel in and out of the cell. There are three types of mediated transporters: uniport, symport, and antiport. Things that can be transported are nutrients, ions, glucose, etc, all depending on the needs of the cell. One example of a uniport mediated transport protein is GLUT1. GLUT1 is a transmembrane protein, which means it spans the entire width of the cell membrane, connecting the extracellular and intracellular region. It is a uniport system because it specifically transports glucose in only one direction, down its concentration gradient across the cell membrane.

In cell biology, microsomes are heterogeneous vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, living cells.

<span class="mw-page-title-main">Calnexin</span> Mammalian protein found in Homo sapiens

Calnexin (CNX) is a 67kDa integral protein (that appears variously as a 90kDa, 80kDa, or 75kDa band on western blotting depending on the source of the antibody) of the endoplasmic reticulum (ER). It consists of a large (50 kDa) N-terminal calcium-binding lumenal domain, a single transmembrane helix and a short (90 residues), acidic cytoplasmic tail.

In biochemistry, lipogenesis is the conversion of fatty acids and glycerol into fats, or a metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipogenesis encompasses both fatty acid and triglyceride synthesis, with the latter being the process by which fatty acids are esterified to glycerol before being packaged into very-low-density lipoprotein (VLDL). Fatty acids are produced in the cytoplasm of cells by repeatedly adding two-carbon units to acetyl-CoA. Triacylglycerol synthesis, on the other hand, occurs in the endoplasmic reticulum membrane of cells by bonding three fatty acid molecules to a glycerol molecule. Both processes take place mainly in liver and adipose tissue. Nevertheless, it also occurs to some extent in other tissues such as the gut and kidney. A review on lipogenesis in the brain was published in 2008 by Lopez and Vidal-Puig. After being packaged into VLDL in the liver, the resulting lipoprotein is then secreted directly into the blood for delivery to peripheral tissues.

Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol, which is sphingosine.

<span class="mw-page-title-main">Phosphatidylethanolamine</span> Group of chemical compounds

Phosphatidylethanolamine (PE) is a class of phospholipids found in biological membranes. They are synthesized by the addition of cytidine diphosphate-ethanolamine to diglycerides, releasing cytidine monophosphate. S-Adenosyl methionine can subsequently methylate the amine of phosphatidylethanolamines to yield phosphatidylcholines.

<span class="mw-page-title-main">Phosphatidylethanolamine N-methyltransferase</span> Protein-coding gene in the species Homo sapiens

Phosphatidylethanolamine N-methyltransferase is a transferase enzyme which converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) in the liver. In humans it is encoded by the PEMT gene within the Smith–Magenis syndrome region on chromosome 17.

<span class="mw-page-title-main">Sterol regulatory element-binding protein 1</span> Protein-coding gene in the species Homo sapiens

Sterol regulatory element-binding transcription factor 1 (SREBF1) also known as sterol regulatory element-binding protein 1 (SREBP-1) is a protein that in humans is encoded by the SREBF1 gene.

<span class="mw-page-title-main">Sterol regulatory element-binding protein 2</span> Protein-coding gene in the species Homo sapiens

Sterol regulatory element-binding protein 2 (SREBP-2) also known as sterol regulatory element binding transcription factor 2 (SREBF2) is a protein that in humans is encoded by the SREBF2 gene.

Palmitoyl-CoA hydrolase (EC 3.1.2.2) is an enzyme in the family of hydrolases that specifically acts on thioester bonds. It catalyzes the hydrolysis of long chain fatty acyl thioesters of acyl carrier protein or coenzyme A to form free fatty acid and the corresponding thiol:

<span class="mw-page-title-main">SOAT1</span> Protein-coding gene in the species Homo sapiens

Sterol O-acyltransferase 1, also known as SOAT1, is an enzyme that in humans is encoded by the SOAT1 gene.

<span class="mw-page-title-main">VAPA</span> Protein-coding gene in humans

VAMP-Associated Protein A is a protein that in humans is encoded by the VAPA gene. Together with VAPB and VAPC it forms the VAP protein family. They are integral endoplasmic reticulum membrane proteins of the type II and are ubiquitous among eukaryotes.

<span class="mw-page-title-main">Sodium/hydrogen exchanger 6</span> Protein-coding gene in the species Homo sapiens

Sodium/hydrogen exchanger 6 is an integral membrane protein that in humans is encoded by the SLC9A6 gene. It was originally thought to be a mitochondrial-targeted protein, but subsequent studies have localized it to the plasma membrane and recycling endosomes.

KDEL is a target peptide sequence in mammals and plants located on the C-terminal end of the amino acid structure of a protein. The KDEL sequence prevents a protein from being secreted from the endoplasmic reticulum (ER) and facilitates its return if it is accidentally exported.

Membrane contact sites (MCS) are close appositions between two organelles. Ultrastructural studies typically reveal an intermembrane distance in the order of the size of a single protein, as small as 10 nm or wider, with no clear upper limit. These zones of apposition are highly conserved in evolution. These sites are thought to be important to facilitate signalling, and they promote the passage of small molecules, including ions, lipids and reactive oxygen species. MCS are important in the function of the endoplasmic reticulum (ER), since this is the major site of lipid synthesis within cells. The ER makes close contact with many organelles, including mitochondria, Golgi, endosomes, lysosomes, peroxisomes, chloroplasts and the plasma membrane. Both mitochondria and sorting endosomes undergo major rearrangements leading to fission where they contact the ER. Sites of close apposition can also form between most of these organelles most pairwise combinations. First mentions of these contact sites can be found in papers published in the late 1950s mainly visualized using electron microscopy (EM) techniques. Copeland and Dalton described them as “highly specialized tubular form of endoplasmic reticulum in association with the mitochondria and apparently in turn, with the vascular border of the cell”.

<span class="mw-page-title-main">Supercomplex</span>

Modern biological research has revealed strong evidence that the enzymes of the mitochondrial respiratory chain assemble into larger, supramolecular structures called supercomplexes, instead of the traditional fluid model of discrete enzymes dispersed in the inner mitochondrial membrane. These supercomplexes are functionally active and necessary for forming stable respiratory complexes.

A FFAT motif is a protein sequence motif of six defined amino acids plus neighbouring residues that binds to proteins in the VAP protein family.

<span class="mw-page-title-main">Star related lipid transfer domain containing 3</span>

StAR related lipid transfer domain containing 3(STARD3) is a protein that in humans is encoded by the STARD3 gene. STARD3 also known as metastatic lymph node 64 protein (MLN64) is a late endosomal integral membrane protein involved in cholesterol transport. STARD3 creates membrane contact sites between the endoplasmic reticulum (ER) and late endosomes where it moves cholesterol.

Nir1 or Membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3) is a mammalian protein that localizes to endoplasmic reticulum (ER) and plasma membrane (PM) membrane contact sites (MCS) and aids the transfer of phosphatidylinositol between these two membranes, potentially by recruiting additional proteins to the ER-PM MCS.

References

  1. 1 2 3 4 5 Dolgin, Elie (11 March 2019). "How secret conversations inside cells are transforming biology". Nature. 567 (7747): 162–164. Bibcode:2019Natur.567..162D. doi: 10.1038/d41586-019-00792-9 . PMID   30858558.
  2. 1 2 3 Bayer, Emmanuelle M.; Calì, Tito; Giordano, Francesca; Hamacher-Brady, Anne; Pellegrini, Luca (2019). "EMBO Workshop: Membrane Contact Sites in Health and Disease". Contact. 2: 251525641982593. doi:10.1177/2515256419825931. ISSN   2515-2564. PMC   6544536 . PMID   31157321.
  3. ↑ "Jean Vance | Faculty of Medicine & Dentistry". www.ualberta.ca. Retrieved 12 June 2019.
  4. 1 2 3 Vance, Dennis E. (20 October 2017). "From masochistic enzymology to mechanistic physiology and disease". The Journal of Biological Chemistry. 292 (42): 17169–17177. doi: 10.1074/jbc.X117.815100 . ISSN   0021-9258. PMC   5655497 . PMID   28855256.
  5. ↑ Vance, J. E. (4 November 1988). "Compartmentalization and differential labeling of phospholipids of rat liver subcellular membranes". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 963 (1): 10–20. doi:10.1016/0005-2760(88)90332-3. ISSN   0006-3002. PMID   3140899.
  6. 1 2 Vance, J. E. (5 May 1990). "Phospholipid synthesis in a membrane fraction associated with mitochondria". The Journal of Biological Chemistry. 265 (13): 7248–7256. doi: 10.1016/S0021-9258(19)39106-9 . ISSN   0021-9258. PMID   2332429.
  7. ↑ Vance, J. E. (5 January 1991). "Newly made phosphatidylserine and phosphatidylethanolamine are preferentially translocated between rat liver mitochondria and endoplasmic reticulum". The Journal of Biological Chemistry. 266 (1): 89–97. doi: 10.1016/S0021-9258(18)52406-6 . ISSN   0021-9258. PMID   1898727.
  8. ↑ Rusiñol, A. E.; Cui, Z.; Chen, M. H.; Vance, J. E. (4 November 1994). "A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins". The Journal of Biological Chemistry. 269 (44): 27494–27502. doi: 10.1016/S0021-9258(18)47012-3 . ISSN   0021-9258. PMID   7961664.
  9. ↑ Shiao, Y. J.; Lupo, G.; Vance, J. E. (12 May 1995). "Evidence that phosphatidylserine is imported into mitochondria via a mitochondria-associated membrane and that the majority of mitochondrial phosphatidylethanolamine is derived from decarboxylation of phosphatidylserine". The Journal of Biological Chemistry. 270 (19): 11190–11198. doi: 10.1074/jbc.270.19.11190 . ISSN   0021-9258. PMID   7744750.
  10. 1 2 "Discovery of cellular structure leads to advances in understanding neurodegeneration and cancer | Faculty of Medicine & Dentistry". www.ualberta.ca. Retrieved 16 March 2019.
  11. ↑ Kornmann, Benoît; Currie, Erin; Collins, Sean R.; Schuldiner, Maya; Nunnari, Jodi; Weissman, Jonathan S.; Walter, Peter (24 July 2009). "An ER-mitochondria tethering complex revealed by a synthetic biology screen". Science. 325 (5939): 477–481. Bibcode:2009Sci...325..477K. doi:10.1126/science.1175088. ISSN   1095-9203. PMC   2933203 . PMID   19556461.
  12. ↑ Wiedemann, Nils; Meisinger, Chris; Pfanner, Nikolaus (24 July 2009). "Connecting Organelles". Science. 325 (5939): 403–404. Bibcode:2009Sci...325..403W. doi:10.1126/science.1178016. ISSN   0036-8075. PMID   19628848. S2CID   9171403.
  13. ↑ Lackner, Laura L.; Ping, Holly; Graef, Martin; Murley, Andrew; Nunnari, Jodi (5 February 2013). "Endoplasmic reticulum-associated mitochondria-cortex tether functions in the distribution and inheritance of mitochondria". Proceedings of the National Academy of Sciences of the United States of America. 110 (6): E458–467. doi: 10.1073/pnas.1215232110 . ISSN   1091-6490. PMC   3568303 . PMID   23341591.
  14. ↑ Pinton, Paolo (2018). "Mitochondria-associated membranes (MAMs) and pathologies". Cell Death & Disease. 9 (4): 413. doi:10.1038/s41419-018-0424-1. ISSN   2041-4889. PMC   5856760 . PMID   29549303.
  15. ↑ Vance, Jean E. (4 April 2014). "MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1841 (4): 595–609. doi:10.1016/j.bbalip.2013.11.014. ISSN   0006-3002. PMID   24316057.
  16. 1 2 de Chaves, E. I.; Rusiñol, A. E.; Vance, D. E.; Campenot, R. B.; Vance, J. E. (5 December 1997). "Role of lipoproteins in the delivery of lipids to axons during axonal regeneration". The Journal of Biological Chemistry. 272 (49): 30766–30773. doi: 10.1074/jbc.272.49.30766 . ISSN   0021-9258. PMID   9388216.
  17. ↑ Karten, Barbara; Vance, Dennis E.; Campenot, Robert B.; Vance, Jean E. (2002). "Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons". Journal of Neurochemistry. 83 (5): 1154–1163. doi: 10.1046/j.1471-4159.2002.01220.x . ISSN   0022-3042. PMID   12437586. S2CID   22730142.
  18. ↑ Peake, Kyle B.; Vance, Jean E. (16 March 2012). "Normalization of cholesterol homeostasis by 2-hydroxypropyl-β-cyclodextrin in neurons and glia from Niemann-Pick C1 (NPC1)-deficient mice". The Journal of Biological Chemistry. 287 (12): 9290–9298. doi: 10.1074/jbc.M111.326405 . ISSN   1083-351X. PMC   3308731 . PMID   22277650.
  19. ↑ Posse De Chaves, E. I.; Vance, D. E.; Campenot, R. B.; Kiss, R. S.; Vance, J. E. (30 June 2000). "Uptake of lipoproteins for axonal growth of sympathetic neurons". The Journal of Biological Chemistry. 275 (26): 19883–19890. doi: 10.1074/jbc.275.26.19883 . ISSN   0021-9258. PMID   10867025.
  20. ↑ Hayashi, Hideki; Campenot, Robert B.; Vance, Dennis E.; Vance, Jean E. (2 April 2004). "Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures". The Journal of Biological Chemistry. 279 (14): 14009–14015. doi: 10.1074/jbc.M313828200 . ISSN   0021-9258. PMID   14709547.
  21. ↑ Hayashi, Hideki; Campenot, Robert B.; Vance, Dennis E.; Vance, Jean E. (21 February 2007). "Apolipoprotein E-containing lipoproteins protect neurons from apoptosis via a signaling pathway involving low-density lipoprotein receptor-related protein-1". The Journal of Neuroscience. 27 (8): 1933–1941. doi: 10.1523/JNEUROSCI.5471-06.2007 . ISSN   1529-2401. PMC   6673537 . PMID   17314289.
  22. ↑ Biochemistry of lipids, lipoproteins, and membranes. Vance, Dennis E., Vance, Jean E. (5th ed.). Amsterdam: Elsevier. 2008. ISBN   978-0444532190. OCLC   180880677.{{cite book}}: CS1 maint: others (link)
  23. ↑ "A TRIP to conclude a successful scientific career | Faculty of Medicine & Dentistry". www.ualberta.ca. Retrieved 16 March 2019.
  24. ↑ Sanders, Robert (9 May 2013). "Howard Hughes Medical Institute names three new campus investigators". Berkeley News. Retrieved 15 June 2019.
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