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Protein kinase C restricts transport of carnitine by amino acid transporter ATB0,+ apically localized in the blood–brain barrier

Abstract : Carnitine (3-hydroxy-4-trimethylammoniobutyrate) is necessary for transfer of fatty acids through the inner mitochondrial membrane. Carnitine, not synthesized in the brain, is delivered there through the strongly polarized blood-brain barrier (BBB). Expression and presence of two carnitine transporters - organic cation/carnitine transporter (OCTN2) and amino acid transporter B(0,+) (ATB(0,+)) have been demonstrated previously in an in vitro model of the BBB. Due to potential protein kinase C (PKC) phosphorylation sites within ATB(0,+) sequence, the present study verified effects of this kinase on transporter function and localization in the BBB. ATB(0,+) can be regulated by estrogen receptor α and up-regulated in vitro, therefore its presence in vivo was verified with the transmission electron microscopy. The analyses of brain slices demonstrated ATB(0,+) luminal localization in brain capillaries, confirmed by biotinylation experiments in an in vitro model of the BBB. Brain capillary endothelial cells were shown to control carnitine gradient. ATB(0,+) was phosphorylated by PKC, what correlated with inhibition of carnitine transport. PKC activation did not change the amount of ATB(0,+) present in the apical membrane of brain endothelial cells, but resulted in transporter exclusion from raft microdomains. ATB(0,+) inactivation by a lateral movement in plasma membrane after transporter phosphorylation has been postulated.
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https://hal-univ-artois.archives-ouvertes.fr/hal-02515246
Contributor : Virginie Justin-Labonne <>
Submitted on : Monday, March 23, 2020 - 2:05:18 PM
Last modification on : Wednesday, March 25, 2020 - 3:43:17 PM

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Katarzyna Michalec, Caroline Mysiorek, Mélanie Kuntz, Vincent Berezowski, Andrzej Szczepankiewicz, et al.. Protein kinase C restricts transport of carnitine by amino acid transporter ATB0,+ apically localized in the blood–brain barrier. Archives of Biochemistry and Biophysics, Elsevier, 2014, 554, pp.28-35. ⟨10.1016/j.abb.2014.05.006⟩. ⟨hal-02515246⟩

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