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PMID:17727637

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Citation

Mameza, MG, Lockard, JM, Zamora, E, Hillefors, M, Lavina, ZS and Kaplan, BB (2007) Characterization of the adaptor protein ARH expression in the brain and ARH molecular interactions. J. Neurochem. 103:927-41

Abstract

Previously, pA134 was identified as one of the mRNAs present in the squid giant axon. Comparative sequence analyses revealed that the pA134 gene product manifested significant similarity to the mammalian lipoprotein receptor adaptor protein also known as ARH (autosomal recessive hypercholesterolemia). ARH mRNA and protein displayed very similar pattern of expression throughout the mouse brain. Significant levels of expression were observed in cells with a predominantly neuronal profile in the cerebellum, brainstem, olfactory bulb, hippocampus, and cortex. A yeast two hybrid screen for ARH protein interactions in mouse brain identified the following binders: amyloid precursor-like protein 1, low density lipoprotein receptor-related protein (LRP) 1, LRP8, and GABA receptor-associated protein-like 1. The interactions of ARH with LRP1 and GABA receptor-associated protein-like 1 were subsequently verified by co-immunoprecipitation of the protein complexes from transfected human embryonic kidney cells. The presence of ARH mRNA in axon of primary sympathetic neurons was established by RT-PCR analyses and confirmed by in situ hybridization. Taken together, our data suggest that ARH is a multifunctional protein whose spectrum of function in the brain goes beyond the traditionally known metabolism of lipoproteins, and that ARH may be locally synthesized in the axon.

Links

PubMed Online version:10.1111/j.1471-4159.2007.04854.x

Keywords

Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Axons/metabolism; Axons/ultrastructure; Brain/anatomy & histology; Brain/metabolism; Brain Chemistry/physiology; Cell Line; Cytoskeletal Proteins/metabolism; Decapodiformes/genetics; Decapodiformes/metabolism; Evolution, Molecular; Ganglia, Sympathetic/metabolism; Ganglia, Sympathetic/ultrastructure; Humans; Lipoproteins/metabolism; Membrane Proteins/metabolism; Mice; Molecular Sequence Data; Protein Binding/physiology; RNA, Messenger/metabolism; Rats; Rats, Sprague-Dawley; Receptors, LDL/metabolism; Sequence Homology, Amino Acid; Tumor Suppressor Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:ARH

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:A4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8C142

F

Seeded From UniProt

complete

MOUSE:APLP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8C142

F

Seeded From UniProt

complete

HUMAN:ARH

located_in

GO:0005883: neurofilament

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8C142

C

Seeded From UniProt

complete

MOUSE:ARH

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8R3R8

F

Seeded From UniProt

complete

MOUSE:ARH

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91ZX7

F

Seeded From UniProt

complete

MOUSE:ARH

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q03157

F

Seeded From UniProt

complete

MOUSE:ARH

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ARH

enables

GO:0001540: amyloid-beta binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12023

F

Seeded From UniProt

complete

MOUSE:ARH

located_in

GO:0005883: neurofilament

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:GBRL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8C142

F

Seeded From UniProt

complete

MOUSE:LRP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8C142

F

Seeded From UniProt

complete


See also

References

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