Affinage

SLC18B1

MFS-type transporter SLC18B1 · UniProt Q6NT16

Length
456 aa
Mass
48.9 kDa
Annotated
2026-06-10
13 papers in source corpus 5 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC18B1 encodes the vesicular polyamine transporter (VPAT), which loads polyamines into secretory vesicles to enable their regulated exocytosis across multiple cell types (PMID:25355561, PMID:31800589). Purified human SLC18B1 reconstituted into proteoliposomes actively transports spermine and spermidine by H+ antiport, driven by an electrochemical H+ gradient, and the protein localizes to vesicles in astrocytes where its knockdown lowers cellular polyamine content (PMID:25355561). VPAT also handles monoamines and depends on the V-ATPase-generated H+ gradient; in mast cells it operates upstream of histamine release, with its knockdown abolishing polyamine exocytosis (PMID:32004521). Vesicular, Ca2+-dependent polyamine secretion via VPAT is similarly demonstrated in megakaryoblastic MEG-01 cells and platelets, where release is sensitive to bafilomycin A1 (V-ATPase inhibition), reserpine, and VPAT inhibitors (PMID:38527572). In vivo, Slc18b1 knockout mice show reduced brain polyamine content, impaired short- and long-term memory, altered expression of LTP/calcium-signalling/synaptic genes, and partial diazepam resistance, establishing VPAT as required for normal brain polyamine homeostasis and GABAergic/glutamatergic signalling (PMID:31800589).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2009 Low

    Established SLC18B1 (C6ORF192) as a distinct solute carrier within the Major Facilitator Superfamily and mapped its tissue expression, framing it as an orphan transporter candidate before any substrate was known.

    Evidence Phylogenetic analysis, qRT-PCR, and in situ hybridization across CNS and peripheral tissues

    PMID:19697161

    Open questions at the time
    • No functional transport or biochemical assay performed
    • Substrate identity entirely unresolved at this stage
    • Subcellular localization not determined
  2. 2014 High

    Resolved the orphan status by showing purified SLC18B1 directly transports spermine and spermidine via H+ antiport, defining it as the vesicular polyamine transporter (VPAT).

    Evidence Proteoliposome reconstitution with purified human protein, in vitro transport assay, vesicular immunolocalization in astrocytes, and siRNA knockdown with polyamine readout

    PMID:25355561

    Open questions at the time
    • Physiological role beyond astrocytes not addressed
    • Coupling stoichiometry and structural basis of antiport not defined
  3. 2019 High

    Demonstrated that VPAT is required in vivo for brain polyamine homeostasis and normal cognition, linking vesicular polyamine handling to memory and inhibitory/excitatory neurotransmission.

    Evidence Slc18b1 knockout mouse with brain polyamine measurement, multiple behavioral paradigms, brain RNA-seq, and diazepam locomotor assay

    PMID:31800589

    Open questions at the time
    • Cell-type origin of the behavioral phenotypes not dissected
    • Mechanistic link between reduced polyamines and altered GABAergic/glutamatergic genes not established
    • No human disease association tested
  4. 2020 High

    Broadened substrate scope to include monoamines and placed VPAT upstream of histamine release in mast cells, connecting polyamine transport to immune secretory output.

    Evidence Proteoliposome transport assay plus siRNA knockdown in mast cells with polyamine exocytosis and histamine secretion measurement

    PMID:32004521

    Open questions at the time
    • Mechanism by which polyamine exocytosis controls histamine release not defined
    • Relative physiological contribution of monoamine vs polyamine transport unclear
  5. 2024 Medium

    Extended VPAT-dependent vesicular polyamine secretion to megakaryoblasts and platelets, showing it is Ca2+- and V-ATPase-dependent in hemostatic cell types.

    Evidence Expression profiling, agonist (A23187/thrombin) stimulation, pharmacological inhibition (bafilomycin A1, reserpine, VPAT inhibitors), and siRNA knockdown in MEG-01 cells and platelets

    PMID:38527572

    Open questions at the time
    • Single-lab cell-based evidence without in vivo confirmation
    • Functional consequence of platelet polyamine release not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How VPAT substrate selectivity, transport stoichiometry, and structural mechanism are determined, and whether SLC18B1 variants cause human disease, remain open.
  • No structural model of the transporter
  • No human Mendelian disease link tested in the timeline
  • Regulation of VPAT expression and vesicular targeting uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0140104 molecular carrier activity 2
Localization
GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-382551 Transport of small molecules 1

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 Purified human SLC18B1 protein reconstituted in proteoliposomes actively transports spermine and spermidine via H+ exchange (antiport), driven by an electrochemical H+ gradient. SLC18B1 is localized to vesicles in astrocytes, and gene knockdown decreased both SLC18B1 protein and spermine/spermidine contents in astrocytes, establishing SLC18B1 as a vesicular polyamine transporter (VPAT). Proteoliposome reconstitution with purified human SLC18B1; in vitro transport assay; immunolocalization to vesicles in astrocytes; siRNA knockdown with polyamine content measurement Scientific reports High 25355561
2020 SLC18B1 (VPAT) transports both monoamines and polyamines (spermidine, spermine) using the electrochemical H+ gradient established by vacuolar H+-ATPase (V-ATPase) as driving force. SLC18B1 gene knockdown abolished polyamine exocytosis from mast cells, which in turn affected histamine secretion, placing VPAT upstream of histamine release. Proteoliposome transport assay; siRNA knockdown in mast cells; polyamine exocytosis measurement; histamine secretion assay Biochimica et biophysica acta. Biomembranes High 32004521
2019 Slc18b1 knockout mice show significantly reduced polyamine content (~20% decrease) in the brain, impaired short- and long-term memory (novel object recognition, radial arm maze, self-administration), altered expression of genes involved in long-term potentiation, calcium signalling, and synaptic function, and partial resistance to diazepam, indicating that VPAT is functionally required for maintaining brain polyamine levels and normal GABAergic/glutamatergic signalling. Slc18b1 knockout mouse model; polyamine content measurement in brain; behavioral tests (novel object recognition, radial arm maze, cocaine self-administration); brain RNA-seq; diazepam locomotor assay PLoS genetics High 31800589
2024 SLC18B1 (VPAT) is expressed in MEG-01 megakaryoblastic cells and platelets. VPAT-mediated vesicular polyamine release from MEG-01 cells is temperature-dependent, Ca2+-dependent, and sensitive to bafilomycin A1 (V-ATPase inhibitor), reserpine, VPAT inhibitors, and VPAT RNA interference, establishing that polyamine secretion from these cells occurs via VPAT-dependent vesicular exocytosis. Platelets also express VPAT and release spermidine upon A23187 and thrombin stimulation. RT-PCR, western blotting, immunohistochemistry for VPAT expression; A23187/thrombin stimulation assay; pharmacological inhibition (bafilomycin A1, reserpine, VPAT inhibitors); siRNA knockdown; polyamine secretion measurement Biochimica et biophysica acta. General subjects Medium 38527572
2009 C6ORF192 (SLC18B1) was identified as a novel solute carrier forming a unique evolutionary branch most closely related to SLC16, SLC17, and SLC18 families within the Major Facilitator Superfamily. It lacks key transmembrane domain motifs shared by those families. Expression profiling (qRT-PCR and in situ hybridization) detected the transcript in multiple CNS regions and peripheral tissues. Phylogenetic/evolutionary analysis; quantitative RT-PCR; in situ hybridization Journal of molecular neuroscience : MN Low 19697161

Source papers

Stage 0 corpus · 13 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Identification of a mammalian vesicular polyamine transporter. Scientific reports 82 25355561
2013 SLC18: Vesicular neurotransmitter transporters for monoamines and acetylcholine. Molecular aspects of medicine 82 23506877
2020 Vesicular polyamine transporter as a novel player in amine-mediated chemical transmission. Biochimica et biophysica acta. Biomembranes 35 32004521
2019 The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain. PLoS genetics 27 31800589
2009 C6ORF192 forms a unique evolutionary branch among solute carriers (SLC16, SLC17, and SLC18) and is abundantly expressed in several brain regions. Journal of molecular neuroscience : MN 14 19697161
2023 Genetic pathways regulating the longitudinal acquisition of cocaine self-administration in a panel of inbred and recombinant inbred mice. Cell reports 11 37481717
2022 A systematic exploration reveals the potential of spermidine for hypopigmentation treatment through the stabilization of melanogenesis-associated proteins. Scientific reports 11 36008447
2018 A transcriptomic signature predicting septic outcome in patients undergoing autologous stem cell transplantation. Experimental hematology 7 29885947
2024 Polyamine release and vesicular polyamine transporter expression in megakaryoblastic cells and platelets. Biochimica et biophysica acta. General subjects 5 38527572
2024 Involvement of mammalian SoLute Carriers (SLC) in the traffic of polyamines. Frontiers in molecular biosciences 5 39130372
2024 Investigating the common genetic architecture and causality of metabolic disorders with neurodegenerative diseases. Diabetes, obesity & metabolism 5 39703124
2024 Polyamine impact on physiology of early stages of reef-building corals-insights from rearing experiments and RNA-Seq analysis. Scientific reports 1 39379401
2026 Genome-Wide Association Study Reveals Insect Genetics and Microbial Symbiont Effects on Susceptibility of Diaphorina citri to the Citrus Greening Pathogen, Candidatus Liberibacter Asiaticus. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41806308

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