Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis

Neuron

Volumn 94, Issue 3, 2017, Pages 581-594.e5

  Andreone, Benjamin J ^a   Chow, Brian Wai ^a   Tata, Aleksandra ^a   Lacoste, Baptiste ^a,d   Ben Zvi, Ayal ^a,e   Bullock, Kevin ^c   Deik, Amy A ^c   Ginty, David D ^a,b   Clish, Clary B ^c   Gu, Chenghua ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^d UNIVERSITY OF OTTAWA   (Canada)

^e HEBREW UNIVERSITY   (Israel)

Author keywords

blood vessels; blood brain barrier; Cav 1; caveolae; CNS endothelial cells; DHA; lipid transport; lipidomic mass spectrometry; Mfsd2a; transcytosis

Indexed keywords

ADULT; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; CAVEOLA; CELL MEMBRANE PERMEABILITY; CELL MIGRATION; CELL VACUOLE; CONTROLLED STUDY; ENDOTHELIUM CELL; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LIPID COMPOSITION; LIPID TRANSPORT; LIPIDOMICS; MALE; MOUSE; NONHUMAN; TRANSCYTOSIS; ANIMAL; CONFOCAL MICROSCOPY; GENETICS; HEK293 CELL LINE; IMMUNOHISTOCHEMISTRY; KNOCKOUT MOUSE; LIPID METABOLISM; METABOLISM; PERMEABILITY; TRANSMISSION ELECTRON MICROSCOPY; ULTRASTRUCTURE; WESTERN BLOTTING;

CARRIER PROTEIN; MFSD2A PROTEIN, MOUSE;

ANIMALS; BLOOD-BRAIN BARRIER; BLOTTING, WESTERN; CAVEOLAE; ENDOTHELIAL CELLS; HEK293 CELLS; HUMANS; IMMUNOHISTOCHEMISTRY; LIPID METABOLISM; MEMBRANE TRANSPORT PROTEINS; MICE; MICE, KNOCKOUT; MICROSCOPY, CONFOCAL; MICROSCOPY, ELECTRON, TRANSMISSION; PERMEABILITY; TRANSCYTOSIS;

EID: 85017463063     PISSN: 08966273     EISSN: 10974199     Source Type: Journal    
DOI: 10.1016/j.neuron.2017.03.043     Document Type: Article

References (56)

1. Aird, W.C., Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ. Res. 100 (2007), 158–173.
2. Alakbarzade, V., Hameed, A., Quek, D.Q., Chioza, B.A., Baple, E.L., Cazenave-Gassiot, A., Nguyen, L.N., Wenk, M.R., Ahmad, A.Q., Sreekantan-Nair, A., et al. A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome. Nat. Genet. 47 (2015), 814–817.
3. Andreone, B.J., Lacoste, B., Gu, C., Neuronal and vascular interactions. Annu. Rev. Neurosci. 38 (2015), 25–46.
4. Armulik, A., Genové, G., Mäe, M., Nisancioglu, M.H., Wallgard, E., Niaudet, C., He, L., Norlin, J., Lindblom, P., Strittmatter, K., et al. Pericytes regulate the blood-brain barrier. Nature 468 (2010), 557–561.
5. Bastiani, M., Parton, R.G., Caveolae at a glance. J. Cell Sci. 123 (2010), 3831–3836.
6. Ben-Zvi, A., Lacoste, B., Kur, E., Andreone, B.J., Mayshar, Y., Yan, H., Gu, C., Mfsd2a is critical for the formation and function of the blood-brain barrier. Nature 509 (2014), 507–511.
7. Betsholtz, C., Physiology: double function at the blood-brain barrier. Nature 509 (2014), 432–433.
8. Bien-Ly, N., Yu, Y.J., Bumbaca, D., Elstrott, J., Boswell, C.A., Zhang, Y., Luk, W., Lu, Y., Dennis, M.S., Weimer, R.M., et al. Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants. J. Exp. Med. 211 (2014), 233–244.
9. Bitsikas, V., Corrêa, I.R. Jr., Nichols, B.J., Clathrin-independent pathways do not contribute significantly to endocytic flux. eLife, 3, 2014, e03970.
10. Brightman, M.W., Reese, T.S., Junctions between intimately apposed cell membranes in the vertebrate brain. J. Cell Biol. 40 (1969), 648–677.
11. Chen, W., Jump, D.B., Esselman, W.J., Busik, J.V., Inhibition of cytokine signaling in human retinal endothelial cells through modification of caveolae/lipid rafts by docosahexaenoic acid. Invest. Ophthalmol. Vis. Sci. 48 (2007), 18–26.
12. Cheng, J.P., Nichols, B.J., Caveolae: one function or many?. Trends Cell Biol. 26 (2016), 177–189.
13. Chow, B.W., Gu, C., The molecular constituents of the blood-brain barrier. Trends Neurosci. 38 (2015), 598–608.
14. Chow, B.W., Gu, C., Gradual suppression of transcytosis governs functional blood-retinal barrier formation. Neuron 93 (2017), 1325–1333.e3.
15. Cohen, A.W., Razani, B., Schubert, W., Williams, T.M., Wang, X.B., Iyengar, P., Brasaemle, D.L., Scherer, P.E., Lisanti, M.P., Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation. Diabetes 53 (2004), 1261–1270.
16. Daneman, R., Zhou, L., Agalliu, D., Cahoy, J.D., Kaushal, A., Barres, B.A., The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells. PLoS ONE, 5, 2010, e13741.
17. Daneman, R., Zhou, L., Kebede, A.A., Barres, B.A., Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468 (2010), 562–566.
18. Ethayathulla, A.S., Yousef, M.S., Amin, A., Leblanc, G., Kaback, H.R., Guan, L., Structure-based mechanism for Na(+)/melibiose symport by MelB. Nat. Commun., 5, 2014, 3009.
19. Ghitescu, L., Fixman, A., Simionescu, M., Simionescu, N., Specific binding sites for albumin restricted to plasmalemmal vesicles of continuous capillary endothelium: receptor-mediated transcytosis. J. Cell Biol. 102 (1986), 1304–1311.
20. Goldstein, G.W., Betz, A.L., Bowman, P.D., Use of isolated brain capillaries and cultured endothelial cells to study the blood-brain barrier. Fed. Proc. 43 (1984), 191–195.
21. Guemez-Gamboa, A., Nguyen, L.N., Yang, H., Zaki, M.S., Kara, M., Ben-Omran, T., Akizu, N., Rosti, R.O., Rosti, B., Scott, E., et al. Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome. Nat. Genet. 47 (2015), 809–813.
22. Guo, Y., Cordes, K.R., Farese, R.V. Jr., Walther, T.C., Lipid droplets at a glance. J. Cell Sci. 122 (2009), 749–752.
23. Haley, M.J., Lawrence, C.B., The blood-brain barrier after stroke: Structural studies and the role of transcytotic vesicles. J. Cereb. Blood Flow Metab. 37 (2017), 456–470.
24. Innis, S.M., Dietary (n-3) fatty acids and brain development. J. Nutr. 137 (2007), 855–859.
25. Junge, H.J., Yang, S., Burton, J.B., Paes, K., Shu, X., French, D.M., Costa, M., Rice, D.S., Ye, W., TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling. Cell 139 (2009), 299–311.
26. Kirkham, M., Fujita, A., Chadda, R., Nixon, S.J., Kurzchalia, T.V., Sharma, D.K., Pagano, R.E., Hancock, J.F., Mayor, S., Parton, R.G., Ultrastructural identification of uncoated caveolin-independent early endocytic vehicles. J. Cell Biol. 168 (2005), 465–476.
27. Knowland, D., Arac, A., Sekiguchi, K.J., Hsu, M., Lutz, S.E., Perrino, J., Steinberg, G.K., Barres, B.A., Nimmerjahn, A., Agalliu, D., Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. Neuron 82 (2014), 603–617.
28. Li, Q., Zhang, Q., Wang, M., Liu, F., Zhao, S., Ma, J., Luo, N., Li, N., Li, Y., Xu, G., Li, J., Docosahexaenoic acid affects endothelial nitric oxide synthase in caveolae. Arch. Biochem. Biophys. 466 (2007), 250–259.
29. Liebner, S., Corada, M., Bangsow, T., Babbage, J., Taddei, A., Czupalla, C.J., Reis, M., Felici, A., Wolburg, H., Fruttiger, M., et al. Wnt/beta-catenin signaling controls development of the blood-brain barrier. J. Cell Biol. 183 (2008), 409–417.
30. Lingwood, D., Simons, K., Lipid rafts as a membrane-organizing principle. Science 327 (2010), 46–50.
31. Ma, D.W., Seo, J., Davidson, L.A., Callaway, E.S., Fan, Y.Y., Lupton, J.R., Chapkin, R.S., n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon. FASEB J. 18 (2004), 1040–1042.
32. Martin, S., Parton, R.G., Caveolin, cholesterol, and lipid bodies. Semin. Cell Dev. Biol. 16 (2005), 163–174.
33. Matsuda, T., Cepko, C.L., Electroporation and RNA interference in the rodent retina in vivo and in vitro. Proc. Natl. Acad. Sci. USA 101 (2004), 16–22.
34. Mayor, S., Parton, R.G., Donaldson, J.G., Clathrin-independent pathways of endocytosis. Cold Spring Harb. Perspect. Biol., 6, 2014, a016758.
35. Nguyen, L.N., Ma, D., Shui, G., Wong, P., Cazenave-Gassiot, A., Zhang, X., Wenk, M.R., Goh, E.L., Silver, D.L., Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature 509 (2014), 503–506.
36. Niewoehner, J., Bohrmann, B., Collin, L., Urich, E., Sade, H., Maier, P., Rueger, P., Stracke, J.O., Lau, W., Tissot, A.C., et al. Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle. Neuron 81 (2014), 49–60.
37. Oh, P., Borgström, P., Witkiewicz, H., Li, Y., Borgström, B.J., Chrastina, A., Iwata, K., Zinn, K.R., Baldwin, R., Testa, J.E., Schnitzer, J.E., Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung. Nat. Biotechnol. 25 (2007), 327–337.
38. Oh, P., Testa, J.E., Borgstrom, P., Witkiewicz, H., Li, Y., Schnitzer, J.E., In vivo proteomic imaging analysis of caveolae reveals pumping system to penetrate solid tumors. Nat. Med. 20 (2014), 1062–1068.
39. Pardridge, W.M., Drug transport across the blood-brain barrier. J. Cereb. Blood Flow Metab. 32 (2012), 1959–1972.
40. Parton, R.G., del Pozo, M.A., Caveolae as plasma membrane sensors, protectors and organizers. Nat. Rev. Mol. Cell Biol. 14 (2013), 98–112.
41. Pike, L.J., Han, X., Chung, K.N., Gross, R.W., Lipid rafts are enriched in arachidonic acid and plasmenylethanolamine and their composition is independent of caveolin-1 expression: a quantitative electrospray ionization/mass spectrometric analysis. Biochemistry 41 (2002), 2075–2088.
42. Pol, A., Martin, S., Fernandez, M.A., Ferguson, C., Carozzi, A., Luetterforst, R., Enrich, C., Parton, R.G., Dynamic and regulated association of caveolin with lipid bodies: modulation of lipid body motility and function by a dominant negative mutant. Mol. Biol. Cell 15 (2004), 99–110.
43. Predescu, S.A., Predescu, D.N., Palade, G.E., Plasmalemmal vesicles function as transcytotic carriers for small proteins in the continuous endothelium. Am. J. Physiol. 272 (1997), H937–H949.
44. Quek, D.Q., Nguyen, L.N., Fan, H., Silver, D.L., Structural insights into the transport mechanism of the human sodium-dependent lysophosphatidylcholine transporter MFSD2A. J. Biol. Chem. 291 (2016), 9383–9394.
45. Razani, B., Engelman, J.A., Wang, X.B., Schubert, W., Zhang, X.L., Marks, C.B., Macaluso, F., Russell, R.G., Li, M., Pestell, R.G., et al. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J. Biol. Chem. 276 (2001), 38121–38138.
46. Reese, T.S., Karnovsky, M.J., Fine structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol. 34 (1967), 207–217.
47. Reiling, J.H., Clish, C.B., Carette, J.E., Varadarajan, M., Brummelkamp, T.R., Sabatini, D.M., A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin. Proc. Natl. Acad. Sci. USA 108 (2011), 11756–11765.
48. Schubert, W., Frank, P.G., Razani, B., Park, D.S., Chow, C.W., Lisanti, M.P., Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo. J. Biol. Chem. 276 (2001), 48619–48622.
49. Shvets, E., Bitsikas, V., Howard, G., Hansen, C.G., Nichols, B.J., Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids. Nat. Commun., 6, 2015, 6867.
50. Sohet, F., Lin, C., Munji, R.N., Lee, S.Y., Ruderisch, N., Soung, A., Arnold, T.D., Derugin, N., Vexler, Z.S., Yen, F.T., Daneman, R., LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation. J. Cell Biol. 208 (2015), 703–711.
51. Stemmer, M., Thumberger, T., Del Sol Keyer, M., Wittbrodt, J., Mateo, J.L., CCTop: an intuitive, flexible and reliable CRISPR/Cas9 target prediction tool. PLoS ONE, 10, 2015, e0124633.
52. Tam, S.J., Richmond, D.L., Kaminker, J.S., Modrusan, Z., Martin-McNulty, B., Cao, T.C., Weimer, R.M., Carano, R.A., van Bruggen, N., Watts, R.J., Death receptors DR6 and TROY regulate brain vascular development. Dev. Cell 22 (2012), 403–417.
53. Zhao, Z., Zlokovic, B.V., Blood-brain barrier: a dual life of MFSD2A?. Neuron 82 (2014), 728–730.
54. Zhao, Z., Nelson, A.R., Betsholtz, C., Zlokovic, B.V., Establishment and dysfunction of the blood-brain barrier. Cell 163 (2015), 1064–1078.
55. Zhou, Y., Wang, Y., Tischfield, M., Williams, J., Smallwood, P.M., Rattner, A., Taketo, M.M., Nathans, J., Canonical WNT signaling components in vascular development and barrier formation. J. Clin. Invest. 124 (2014), 3825–3846.
56. Zlokovic, B.V., The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57 (2008), 178–201.