Isolation and cloning of a voltage-dependent anion channel-like Mr 36,000 polypeptide from mammalian brain.

Bureau, M.; Khrestchatisky, Michel; Heeren, M A; Zambrowicz, Ewa Brygida; Kim, H; Grisar, Thierry; Colombini, Marco; Tobin, Allan J.; Olsen, Richard W.

doi:10.1016/s0021-9258(18)42496-9

Cited by 85 publications

(4 citation statements)

References 39 publications

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“…However, two proteins were detected with both the α1 and α4 subunits in our findings: Myo5a and Vdac2. Myo5a has been implicated in subcellular localization of gephyrin ( Fuhrmann et al, 2002 ) and Vdac2 has been found to associate with GABA A Rs ( Bureau et al, 1992 ; Darbandi-Tonkabon et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Analyzing the mechanisms that facilitate the subtype-specific assembly of γ-aminobutyric acid type A receptors

Choi

Smalley

Lemons

et al. 2022

Front. Mol. Neurosci.

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Impaired inhibitory signaling underlies the pathophysiology of many neuropsychiatric and neurodevelopmental disorders including autism spectrum disorders and epilepsy. Neuronal inhibition is regulated by synaptic and extrasynaptic γ-aminobutyric acid type A receptors (GABAARs), which mediate phasic and tonic inhibition, respectively. These two GABAAR subtypes differ in their function, ligand sensitivity, and physiological properties. Importantly, they contain different α subunit isoforms: synaptic GABAARs contain the α1–3 subunits whereas extrasynaptic GABAARs contain the α4–6 subunits. While the subunit composition is critical for the distinct roles of synaptic and extrasynaptic GABAAR subtypes in inhibition, the molecular mechanism of the subtype-specific assembly has not been elucidated. To address this issue, we purified endogenous α1- and α4-containing GABAARs from adult murine forebrains and examined their subunit composition and interacting proteins using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and quantitative analysis. We found that the α1 and α4 subunits form separate populations of GABAARs and interact with distinct sets of binding proteins. We also discovered that the β3 subunit, which co-purifies with both the α1 and α4 subunits, has different levels of phosphorylation on serines 408 and 409 (S408/9) between the two receptor subtypes. To understand the role S408/9 plays in the assembly of α1- and α4-containing GABAARs, we examined the effects of S408/9A (alanine) knock-in mutation on the subunit composition of the two receptor subtypes using LC-MS/MS and quantitative analysis. We discovered that the S408/9A mutation results in the formation of novel α1α4-containing GABAARs. Moreover, in S408/9A mutants, the plasma membrane expression of the α4 subunit is increased whereas its retention in the endoplasmic reticulum is reduced. These findings suggest that S408/9 play a critical role in determining the subtype-specific assembly of GABAARs, and thus the efficacy of neuronal inhibition.

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Section: Discussionmentioning

confidence: 99%

Analyzing the mechanisms that facilitate the subtype-specific assembly of γ-aminobutyric acid type A receptors

Choi

Smalley

Lemons

et al. 2022

Front. Mol. Neurosci.

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“…In preliminary studies, we have obtained a sequence (APAPTPAPAPEXVK) of a peptide fragment obtained from the LYS-C digest of DNP-SG ATPase. Proline-rich sequences such as this are known to be present in channel-forming β-strand domains of other proteins including porins ( 22), R-ketoacid dehydrogenase complex (23), and photoreceptor cGMP-gated channel (24). Aliquots of transport buffer (30 µL) were filtered in triplicate after 5 min.…”

Section: Discussionmentioning

confidence: 99%

ATP-Dependent Human Erythrocyte Glutathione-Conjugate Transporter. II. Functional Reconstitution of Transport Activity

et al. 1998

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Purified dinitrophenyl S-glutathione (DNP-SG) ATPase was reconstituted into artificial liposomes prepared from soybean asolectin. Electron micrography confirmed the formation of unilamellar vesicles with an average radius of 0.25 micron. Intravesicular volume estimated by incorporation of radiolabled inulin into the vesicles was found to be 19.7 +/- 1.3 microL/mL reconstitution solution. Accumulation of the glutathione-conjugate of CDNB, DNP-SG, and of doxorubicin (DOX) in the proteoliposomes was increased in the presence of ATP as compared to equimolar ADP or adenosine 5'-[beta,gamma-methylene]triphosphate tetralithium. ATP-dependent transmembrane movement of DOX and DNP-SG into DNP-SG ATPase-reconstituted vesicles was saturable with respect to time, sensitive to the osmolarity of the assay medium, and temperature dependent. The energy of activation was found to be 12 and 15 kcal/mol for DNP-SG and DOX, respectively. Optimal temperature for transport was 37 degrees C. Saturable transport was demonstrated for DNP-SG (Vmax of 433 +/- 20 nmol/min/mg of protein, KmATP = 2.4 +/- 0. 3 mM and KmDNP-SG = 36 +/- 5 microM) as well as DOX (Vmax = 194 +/- 19 nmol/min/mg of protein, KmATP = 2.5 +/- 0.6 mM and KmDOX = 2.4 +/- 0.7 microM). The kinetic data for both DNP-SG and DOX transport were consistent with a random bi-bi sequential reaction mechanism. DOX was found to be a competitive inhibitor of DNP-SG transport with Kis of 1.2 +/- 0.2 microM and DNP-SG was found to be a competitive inhibitor of DOX transport with Kis of 13.3 +/- 2.6 microM.

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“…The voltage dependence of mitochondrial porins from a variety of eukaryotic organisms was investigated in detail in many studies: Paramecium [ 9 , 102 , 104 ]; mammals including rats [ 16 , 18 , 36 ], rabbits [ 35 ], bovine [ 35 ], pigs [ 35 ], and the human brain [ 105 ]; fish including Anguilla anguilla [ 99 ]; plants including Arabidopsis [ 106 ], potatoes [ 45 , 63 ], peas [ 46 ], corn [ 46 , 107 , 108 ], wheat [ 95 ], and pea root plastid porin [ 46 , 69 ]; other organisms including Neurospora crassa [ 15 ], yeast [ 37 , 51 , 91 ], Dictyostelium [ 53 ]; and flies including Protophormia [ 101 ] and Drosophila [ 58 , 92 , 109 ]. Common to all the pores investigated in these studies is that the mitochondrial porins of all these eukaryotes formed high-conducting channels in reconstituted systems.…”

Section: Electrophysiology Of Mitochondrial Porinsmentioning

confidence: 99%

Solute Transport through Mitochondrial Porins In Vitro and In Vivo

Benz

2024

Biomolecules

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Mitochondria are most likely descendants of strictly aerobic prokaryotes from the class Alphaproteobacteria. The mitochondrial matrix is surrounded by two membranes according to its relationship with Gram-negative bacteria. Similar to the bacterial outer membrane, the mitochondrial outer membrane acts as a molecular sieve because it also contains diffusion pores. However, it is more actively involved in mitochondrial metabolism because it plays a functional role, whereas the bacterial outer membrane has only passive sieving properties. Mitochondrial porins, also known as eukaryotic porins or voltage-dependent anion-selective channels (VDACs) control the permeability properties of the mitochondrial outer membrane. They contrast with most bacterial porins because they are voltage-dependent. They switch at relatively small transmembrane potentials of 20 to 30 mV in closed states that exhibit different permeability properties than the open state. Whereas the open state is preferentially permeable to anionic metabolites of mitochondrial metabolism, the closed states prefer cationic solutes, in particular, calcium ions. Mitochondrial porins are encoded in the nucleus, synthesized at cytoplasmatic ribosomes, and post-translationally imported through special transport systems into mitochondria. Nineteen beta strands form the beta-barrel cylinders of mitochondrial and related porins. The pores contain in addition an α-helical structure at the N-terminal end of the protein that serves as a gate for the voltage-dependence. Similarly, they bind peripheral proteins that are involved in mitochondrial function and compartment formation. This means that mitochondrial porins are localized in a strategic position to control mitochondrial metabolism. The special features of the role of mitochondrial porins in apoptosis and cancer will also be discussed in this article.

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Isolation and cloning of a voltage-dependent anion channel-like Mr 36,000 polypeptide from mammalian brain.

Cited by 85 publications

References 39 publications

Analyzing the mechanisms that facilitate the subtype-specific assembly of γ-aminobutyric acid type A receptors

Analyzing the mechanisms that facilitate the subtype-specific assembly of γ-aminobutyric acid type A receptors

ATP-Dependent Human Erythrocyte Glutathione-Conjugate Transporter. II. Functional Reconstitution of Transport Activity

Solute Transport through Mitochondrial Porins In Vitro and In Vivo

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