SLC7A3 — Cationic Amino Acid Transporter 3

SLC7A3 — Cationic Amino Acid Transporter 3

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC7A3 — Cationic Amino Acid Transporter 3</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SLC7A3</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Cationic Amino Acid Transporter 3 (CAT3)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>Xq28</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[6534](https://www.ncbi.nlm.nih.gov/gene/6534)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[300443](https://www.omim.org/entry/300443)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000165370</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q8WWI5](https://www.uniprot.org/uniprot/Q8WWI5)</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

{{.infobox .infobox-gene}}

Overview

SLC7A3 — Cationic Amino Acid Transporter 3

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC7A3 — Cationic Amino Acid Transporter 3</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SLC7A3</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Cationic Amino Acid Transporter 3 (CAT3)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>Xq28</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[6534](https://www.ncbi.nlm.nih.gov/gene/6534)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[300443](https://www.omim.org/entry/300443)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000165370</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q8WWI5](https://www.uniprot.org/uniprot/Q8WWI5)</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

{{.infobox .infobox-gene}}

Overview

SLC7A3 (Solute Carrier Family 7 Member 3), also known as Cationic Amino Acid Transporter 3 (CAT3), is a human gene encoding a high-affinity cationic amino acid transporter protein. This transporter is primarily responsible for the uptake of cationic amino acids, particularly arginine and lysine, into cells. SLC7A3 is expressed predominantly in the developing and adult brain, where it plays critical roles in neuronal development, synaptic function, and nitric oxide (NO) signaling[@ito1997][@closs2001]. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Molecular Function

Cationic Amino Acid Transport

SLC7A3 encodes a member of the system y+ family of cationic amino acid transporters[cat1_function2010]. The transporter exhibits high affinity for cationic amino acids:

Substrate Specificity: CAT3 primarily transports:

• L-Arginine (highest affinity)
• L-Lysine
• L-Ornithine
• L-Histidine (lower affinity)

System y+ Transport

The SLC7 family includes multiple cationic amino acid transporters (CAT1-4), each with distinct expression patterns and functional properties[system_y_plus2012]:

• SLC7A1 (CAT1): Widely expressed, essential for vascular arginine transport
• SLC7A2 (CAT2): Inducible, important in inflammation
• SLC7A3 (CAT3): Neuron-specific, high-affinity arginine transporter
• SLC7A4 (CAT4): Lower affinity, broader substrate range

Role in Nitric Oxide Synthesis

One of the most important functions of CAT3 in the brain is providing arginine substrate for nitric oxide synthase (NOS)[hatanaka2008]:

Nitric Oxide Signaling: Arginine is the sole substrate for nitric oxide synthesis by neuronal nitric oxide synthase (nNOS). CAT3-mediated arginine uptake is therefore essential for NO production in neurons.

nNOS Activation: Neuronal activity triggers nNOS activation, which requires rapid arginine replenishment. CAT3's high-affinity transport ensures adequate substrate availability during signaling events[nakamura2017].

NO Functions in the Brain: Nitric oxide serves as a:

• Neurotransmitter/neuromodulator
• Regulator of cerebral blood flow
• Mediator of synaptic plasticity
• Second messenger in learning and memory

Role in Brain Development

Developmental Expression

SLC7A3 is highly expressed during brain development, particularly in neuronal populations[hosokawa2002][@kikuchi2013]:

Embryonic Expression: During embryogenesis, CAT3 is expressed in neural progenitor cells and newly differentiated neurons. The transporter appears early in development and peaks during periods of active neurogenesis.

Postnatal Development: SLC7A3 expression continues to increase postnatally, corresponding to:

• Synaptogenesis
• Dendritic arborization
• Myelination

Neuronal Differentiation

CAT3 plays a role in neuronal differentiation through several mechanisms[agarwal2014]:

Arginine Availability: Adequate intracellular arginine is required for:

• Protein synthesis during neurite outgrowth
• Polyamine synthesis (putrescine, spermidine, spermine)
• Nitric oxide signaling during differentiation

Brain Patterning

Studies in knockout mice have revealed important roles for SLC7A3 in brain development[stork2005]:

• Normal cortical layering
• Hippocampal formation
• Cerebellar development
• Axonal tract development

Expression Pattern

Regional Distribution

SLC7A3 shows region-specific expression in the brain[vekhi2002]:

Hippocampus: High expression in CA1-CA3 pyramidal neurons and dentate gyrus granule cells. The hippocampus shows some of the highest SLC7A3 expression in the adult brain.

Cortex: Expression in pyramidal neurons across all cortical layers, with highest levels in layer V neurons that project to subcortical structures.

Cerebellum: Expression in Purkinje cells and granule cells. The transporter is particularly important in cerebellar development.

Brainstem: Expression in various nuclei including the dorsal raphe (serotonergic) and locus coeruleus (noradrenergic).

Cellular Localization

Within neurons, CAT3 is localized to:

• Soma: Cell body membrane
• Dendrites: Dendritic shaft and spine membranes
• Axon terminals: Presynaptic membranes
• Endoplasmic reticulum: Intracellular pool

Disease Associations

Alzheimer's Disease

Arginine metabolism is increasingly recognized as relevant to Alzheimer's disease pathogenesis[ad_arginine2018]:

Arginine Depletion: AD brains show altered arginine metabolism, with decreased arginine availability in neurons. This may reflect reduced CAT3 function or expression.

nNOS Dysfunction: Nitric oxide signaling is impaired in AD, partly due to substrate limitation. CAT3 dysfunction could contribute to reduced NO production and impaired synaptic plasticity.

Polyamine Metabolism: The polyamine pathway is altered in AD. Since arginine is a precursor for polyamines, CAT3 dysfunction may affect this important metabolic pathway.

Excitotoxicity: Arginine transport influences glutamate receptor function and excitotoxicity[glutamate_excitotoxicity2008]. CAT3 may protect neurons from excitotoxic damage.

Parkinson's Disease

Arginine metabolism is also altered in Parkinson's disease[pd_arginine2019]:

Dopaminergic Neurons: The substantia nigra pars compacta (SNc) shows specific vulnerabilities that may relate to arginine transport. CAT3 expression in dopaminergic neurons may be relevant to their survival.

nNOS Expression: nNOS is expressed in dopaminergic neurons and can produce cytotoxic levels of NO under certain conditions. CAT3-mediated arginine uptake may influence this balance.

Mitochondrial Function: Arginine metabolism affects mitochondrial function through NO signaling. CAT3 dysfunction may contribute to mitochondrial impairment in PD.

Neurodevelopmental Disorders

Given its role in brain development, SLC7A3 variants may contribute to neurodevelopmental disorders:

• Intellectual disability
• Autism spectrum disorders
• Schizophrenia

Neuropsychiatric Disorders

Altered SLC7A3 expression or function has been implicated in:

• Depression (through NO signaling)
• Anxiety disorders
• Drug addiction (through mesolimbic dopamine system)

Key Research Findings

Knockout Mouse Studies

Comprehensive studies in CAT3 knockout mice have revealed[ nakamura2017]:

Gene Expression Changes: Whole-genome expression analysis of knockout brains shows:

• Upregulation of stress response genes
• Altered synaptic function genes
• Changes in cell death/survival pathways

• Learning and memory deficits
• Altered stress responses
• Motor coordination issues

• Reduced nNOS activity
• Altered polyamine levels
• Changed neurotransmitter levels

Human Studies

Human brain studies have characterized SLC7A3 expression[vekhi2002]:

• Protein is detectable in neurons throughout the brain
• Regional patterns mirror mouse expression
• Changes in disease states are being characterized

Therapeutic Implications

Targeting Arginine Transport

Modulating SLC7A3 function could have therapeutic applications:

Arginine Supplementation: Increasing extracellular arginine availability could compensate for reduced transport in disease states.

NOS Modulation: Since CAT3 provides substrate for nNOS, modulating its activity could influence NO signaling in specific contexts.

Blood-Brain Barrier: Understanding CAT3's role at the blood-brain barrier[blood_brain_barrier2007] could inform drug delivery strategies.

Amino Acid-Based Therapies

Given the importance of arginine transport in brain function:

NO-Based Therapies: Modulating NO production through arginine availability could influence:

• Cerebral blood flow
• Synaptic plasticity
• Neuroprotection

See Also

• [Amino Acid Transporters](/mechanisms/amino-acid-transport)
• [Nitric Oxide Signaling](/mechanisms/nitric-oxide-signaling)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Hippocampus](/brain-regions/hippocampus)
• [Cortex](/brain-regions/cortex)
• [Neurons](/entities/neurons)

Related Pages

• [Genes Directory](/genes/)
• [Neurodegeneration Pathways](/diseases/neurodegeneration)
• [SLC Family Transporters](/proteins/slc-transporters)

External Links

• [NCBI Gene: SLC7A3](https://www.ncbi.nlm.nih.gov/gene/6534)
• [OMIM Entry: 300443](https://www.omim.org/entry/300443)
• [Ensembl: SLC7A3](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000165370)
• [UniProt: Q8WWI5](https://www.uniprot.org/uniprot/Q8WWI5)
• [GeneCards: SLC7A3](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC7A3)

References