Disease relevance of Slc7a1

• Thus, mCAT-1 not only appears to be the sole receptor for a group of murine ecotropic retroviruses associated with hematological disease but also plays a critical role in both hematopoiesis and growth control during mouse development [1].
• The product of the mouse Rec-1 locus is an integral membrane protein that determines susceptibility to infection by murine ecotropic retroviruses [2].
• This sequence also exhibited 14 base changes compared with the sequence of ecotropic retrovirus receptor (ERR)/CAT-1 from rat hepatoma [3].
• To analyze the ecotropic receptor, CAT1, in XC cells, a mouse CAT1 tagged with the influenza virus hemagglutinin epitope (mCAT1-HA)-expressing retroviral vector was inoculated into XC and NIH 3T3 cells [4].
• Only the neutralizing MAbs specific for the receptor-binding pocket were able to block binding of purified SU and MuLV virions to cells expressing the ecotropic MuLV receptor, mCAT-1 [5].

Psychiatry related information on Slc7a1

• Unexpectedly, CAT2a transcripts accumulated in skeletal muscle in response to surgical trauma (hepatectomy and splenectomy) as well as food deprivation, although neither high affinity CAT2 nor CAT1 were detectably altered [6].

High impact information on Slc7a1

• The data are consistent with a model for receptor co-operativity in which binding to the targeted (Ram-1) receptor triggers conformational rearrangements of the envelope that lead to complete unmasking of the hidden Rec-1-binding domain, thereby facilitating its interaction with the viral (Rec-1) receptor which leads to optimal fusion triggering [7].
• The mCAT-2 protein sequence is closely related to another cationic AA transporter (mCAT-1); these related proteins elicit virtually identical cationic AA transport in Xenopus oocytes [8].
• The Tea gene is distinct from, but bears extensive amino acid and DNA sequence similarity with, the murine ecotropic retroviral receptor which is encoded by the Rec-1 gene [9].
• These results suggest that Cat3 compensates for the loss of functional Cat1 in cells derived from Cat1 knockout mice and mediates the majority of high affinity arginine transport [10].
• Even though Cat3 expression is normally limited to adult brain, there was a large increase in the amount of Cat3 protein present at the plasma membrane of Cat1(-/-) embryonic fibroblast cells [10].

Chemical compound and disease context of Slc7a1

• CONCLUSIONS: Gentamicin may be used along with doxycycline when the classical combination is considered the first choice in the treatment of patients with brucellosis due to B. melitensis vaccine strain Rev 1 [11].
• OBJECTIVES: The objective of the present study was to compare the efficacy of gentamicin given alone or combined with doxycycline with that of standard combination therapies in BALB/c mice experimentally infected with the Brucella melitensis vaccine strain Rev 1 [11].
• Insertion of targeting domains into the envelope glycoprotein of Moloney murine leukemia virus (MoMLV)-based vectors modulates the route of mCAT-1-mediated viral entry [12].

Biological context of Slc7a1

• We show that this sequence is likely to be Rec-1, the chromosome 5 locus originally defined by studies with somatic cell hybrids as responsible for virus susceptibility, and provide a specific chromosomal map position for this locus by analysis of an interspecies backcross [13].
• Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles [14].
• Transient transfection of ecotropic retrovirus receptor permits stable gene transfer into non-rodent cells with murine retroviral vectors [15].
• These results suggest that N-linked glycosylation causes wild-type mCAT-1 heterogeneity and that a significant proportion is inaccessible to virus [16].
• However, the pathogenicity was unaltered when the env gene is exchanged with Moloney MuLV, which uses the Cat1 receptor [17].

Anatomical context of Slc7a1

• In the present study, we raised a polyclonal antibody against CAT-1, and show using reciprocal co-immunoprecipitation protocols that eNOS and CAT-1 do indeed form a complex in BAECs (bovine aortic endothelial cells) [18].
• Increased Cat3-mediated cationic amino acid transport functionally compensates in Cat1 knockout cell lines [10].
• Our data establish CAT-1 as a major determinant of ecotropic retrovirus infection in rodent hepatocytes and suggest that CAT-2 is not a receptor for viruses in the amphotropic subgroup [19].
• Because this serine residue is one of the critical amino acids that form the CAT-1 receptor binding site, and because M. dunni and hamster cells have variant CAT-1 receptors, these results suggest that syncytium formation as well as altered host range may be a consequence of altered interaction between virus and receptor [20].
• CAT-1 was expressed in both cell types, whereas CAT-2B was only expressed in activated macrophages [21].

Associations of Slc7a1 with chemical compounds

• Overexpression of CAT-1 in BAECs by adenoviral-mediated gene transfer results in significant increases in both L-arginine uptake and NO production by the cells [18].
• However, whereas increased L-arginine transport is reversed completely by the CAT-1 inhibitor, L-lysine, increased NO release is unaltered, suggesting that NO production in this in vitro model is independent of CAT-1-mediated transport [18].
• In vitro binding assays with GST (glutathione S-transferase)-CAT-1 fusion proteins and eNOS show that the two proteins interact directly and that no single CAT-1 intracellular domain is sufficient to mediate the interaction [18].
• Bindings of ecotropic envelope glycoprotein gp7O to the accessible receptor sites on surfaces of mink cells expressing wild-type or mutant mCAT-1 were not significantly different in kinetics or in equilibrium affinities (i.e., K(D) approximately 3.7 X 10(-10) to 7.5 X 10(-10) M) [16].
• The R(+) Env protein induced syncytia in XC cells expressing a mutant mCAT1 lacking both of two N glycosylation sites, and tunicamycin treatment suppressed syncytium formation by R(+) Env in those cells [4].

Regulatory relationships of Slc7a1

• B. melitensis Rev 1 (2.2 x 10(5) c.f.u.) and B. suis strain 2 (1.2 x 10(7) c.f.u.) live vaccines but not the inactivated B. melitensis H38 vaccine conferred protection against B. ovis [22].

Other interactions of Slc7a1

• In situ hybridization on brain sections revealed that CAT3 transcripts were localized predominantly along the midbrain-thalamus-hypothalamus axis, whereas neither CAT1 nor CAT2 transcripts demonstrated a similar localization [23].
• SLC7A1/Cat1 is constitutively expressed, and is not modified by proliferating or activating agents [24].
• The expression of CAT1, CAT3, y+ LAT1 and y+ LAT2 mRNAs supports the presence of each system [25].
• AMOPRO viruses could not enter cells expressing only Rec-1 or only Ram-1 but could efficiently infect cells co-expressing both receptors [7].
• Our data revealed that LPS co-induced iNOS, CAT-2, and CAT-2B expression, whereas CAT-1 and CAT-2A expression remained unaffected [26].

Analytical, diagnostic and therapeutic context of Slc7a1

• Using reverse transcription-coupled polymerase chain reaction methodology, a partial cDNA with 94% sequence identity to that of cationic amino acid transporter subtype-1 (CAT-1) of mouse fibroblasts was obtained from VSMC [3].
• Vaccination against Brucella infections in animals is usually performed by administration of live attenuated smooth B. abortus strain S19 and B. melitensis strain Rev1 [27].
• Distribution of ecotropic retrovirus receptor protein in rat brains detected by immunohistochemistry [28].
• As with the wild-type mCAT1 and rCAT1 proteins, the rCAT1 mutants were detected on the cell surface by immunofluorescence microscopy [29].
• To determine whether repeated passage would select for functional variants of the receptor, we analyzed mCAT1 amplified by RT-PCR after 12 serial passages [30].

References