Disease relevance of ATRN

• Expression of attractin and its differential enzyme activity in glioma cells [1].
• Defective surface expression of attractin on T cells in patients with common variable immunodeficiency (CVID) [2].

High impact information on ATRN

• Secreted and membrane attractin result from alternative splicing of the human ATRN gene [3].
• The mRNA isoform for membrane attractin splices over the LINE-1 exon and includes five exons encoding transmembrane and cytoplasmic domains with organization and coding potential almost identical to that of the mouse gene [3].
• The genomic structure of human attractin reveals that soluble attractin arises from transcription of 25 sequential exons on human chromosome 20p13, where the 3' terminal exon contains sequence from a long interspersed nuclear element-1 (LINE-1) retrotransposon element that includes a stop codon and a polyadenylation signal [3].
• We have cloned attractin and find that, as in its natural serum form, it mediates the spreading of monocytes that become the focus for the clustering of nonproliferating T lymphocytes [4].
• Attractin (DPPT-L), a member of the CUB family of cell adhesion and guidance proteins, is secreted by activated human T lymphocytes and modulates immune cell interactions [4].

Biological context of ATRN

• Except for the latter two domains, the overall structure shares high homology with the Caenorhabditis elegans F33C8.1 protein, suggesting that attractin has evolved new domains and functions in parallel with the development of cell-mediated immunity [4].
• Transcription of attractin secreted form mRNA is strongly downregulated upon differentiation of a human cortical neuron-derived cell line (HCN-1A) to a mature neuron phenotype in response to nerve growth factor [5].
• Due to the likely role of attractin in cell guidance and amplification of the immune response, our results indicate that the lack of up-regulation of the molecule in patients with CVID may in turn affect any further step of productive immune response [2].
• The discovery that a transmembrane form not only controls neuropeptide regulation of hair pigmentation in animals but also affects basal metabolism led to proposals that attractin may also be an extracellular target amenable for the development of obesity-regulating drugs [6].

Anatomical context of ATRN

• Recombinant secreted attractin disrupts neurite formation by differentiated HCN-1A cells, resulting in higher levels of branching with shorter processes [5].
• Mutations at the Atrn locus that encodes a transmembrane protein with a large ectodomain are responsible for a juvenile-onset neurodegeneration manifest as hypomyelination and cerebral vacuole development in several rodent species [5].
• We report here that the secreted form mRNA is downregulated throughout representative discrete regions of the human brain while membrane attractin mRNA is well represented, resulting in the apparent absence of secreted attractin protein in cerebrospinal fluid (CSF) [5].
• In the central nervous system, attractin has been detected in neurons but not in glial cells up to now [1].

Regulatory relationships of ATRN

• The loss of DPPT-L from the surface of activated T cells correlates exactly with the appearance of DPPT-L and DPPIV activity in serum-free tissue culture medium [7].
• On control cells, however, attractin expression was up-regulated together with CD25 and CD26 [2].

Other interactions of ATRN

• Serum high molecular weight dipeptidyl peptidase IV (CD26) is similar to a novel antigen DPPT-L released from activated T cells [7].

Analytical, diagnostic and therapeutic context of ATRN

• In contrast, the native electrophoretic behavior of this activity is clearly different from human and porcine DP4, but co-migrates with the protein band identified as attractin by Western blotting and N-terminal sequencing [8].
• Nevertheless, a DP4 impurity could be demonstrated in purified plasma attractin and the activity could be removed by ADA affinity chromatography, resulting in a homogenous attractin preparation without DP4 activity [8].

References