Disease relevance of DPYSL5

• CRMP-5 is in adult central and peripheral neurons, including synapses, and in small-cell lung carcinomas [1].
• CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity [1].
• Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma [2].
• Clinicians use many terms including undulating myokymia, neuromyotonia, Isaacs' syndrome and Cramp-Fasciculation Syndrome to describe the motor manifestations of generalized peripheral nerve hyperexcitability (PNH) [3].
• Other serological markers, such as collapsin response-mediator protein-5 -IgG and amphiphysin-IgG, predict specific cancers in the setting of a paraneoplastic acute transverse myelitis [4].

High impact information on DPYSL5

• Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP-5-specific immunoreactivity [5].
• Full-length CRMP-5 protein was identified in normal retina and optic nerve by Western blot analyses [5].
• We have defined a new paraneoplastic immunoglobulin G (IgG) autoantibody specific for CRMP-5, a previously unknown 62-kd neuronal cytoplasmic protein of the collapsin response-mediator family [1].
• This makes CRMP-5 autoantibody as frequent as PCA-1 (anti-Yo) autoantibody, second only to ANNA-1 (anti-Hu) [1].
• Here we report the identification of a novel CRMP3-associated protein, designated CRAM for CRMP3-associated molecule, that belongs to the unc-33 gene family [6].

Biological context of DPYSL5

• The mouse CRMP5 gene was located at chromosome 5 B1 [7].

Anatomical context of DPYSL5

• Like Ulip1-4, Ulip6 is highly expressed in embryonic and early postnatal brain and spinal cord [8].
• Thus, the normal CRMP5 is probably not expressed by tumorous epithelial cells [9].
• Expression of the onconeural CV2/CRMP5 antigen in thymus and thymoma [9].
• However, they remain expressed in structures that retain their capacity for differentiation and plasticity and also in a subpopulation of oligodendrocytes (CRMP2 and CRMP5) [10].
• In the adult, Ulip6/CRMP5 is still expressed in some neurons, namely in areas that retain neurogenesis and in oligodendrocytes in the midbrain, hindbrain, and spinal cord [11].

Associations of DPYSL5 with chemical compounds

• Neuronal autoantibody specificities were, in descending order of frequency, as follows: glutamic acid decarboxylase, voltage-gated potassium channel, collapsin response-mediator protein-5, ganglionic AChR, and antineuronal nuclear antibody-type 1 (ANNA-1) [12].
• The epoxide moiety in 1 was generated by regioselective mesylation and base treatment of the 12,13-diol 30 which was formed by a chelate Cram controlled Grignard addition of 14 and methyl ketone 13 [13].
• A comparison was made between this new and virtually unused method and our earlier reported results using Cram methodology (reaction of aryl iodide with potassium tert-butoxide) [14].
• Paraneoplastic autonomic disorders are clinically indistinguishable and associated with various overlapping antibody associations, including anti-Hu (ANNA-1), ganglionic acetylcholine receptors, CRMP-5, and PCA-2 [15].
• We use molecular mechanics to calculate the conformational properties of a cyclic urea mimetic of alpha-chymotrypsin proposed, but not yet synthesized, by Cram and co-workers [16].

Other interactions of DPYSL5

• In the presence of Sema3A, these oligodendrocytes displayed a dramatic reduction in process extension, which was reversed by removal of Sema3A and prevented by anti-neuropilin-1, anti-Ulip6/CRMP5, anti-Ulip2/CRMP2 antibodies, or VEGF-165, another neuropilin-1 ligand [11].
• C. neoformans encodes a single member of the Nramp (natural resistance-associated macrophage protein) family of bivalent cation transporters, known as Cramp, which we have cloned and expressed in Xenopus laevis oocytes and Spodoptera frugiperda Sf 21 insect cells [17].

Analytical, diagnostic and therapeutic context of DPYSL5

• In this study, we cloned a novel member of this family, which we call CRMP5, by the yeast two-hybrid method [7].
• In thymoma, none of the CRMPs were detected by immunohistochemistry in tumorous epithelial cells with specific antibodies including CRMP5 but an antibody reacting with a peptide common to the CRMPs labeled a 66-kDa protein in Western blot of rat brain, thymus, and thymoma extracts [9].
• Serologic tests revealed a neuronal autoantibody specific for CRMP-5, a 62-kd member of the collapsin response-mediating protein family [18].
• Because PIOL has a nonspecific presentation, the differential diagnosis should include infectious and noninfectious causes presenting with vitreitis and/or subepithelial infiltration as well as paraneoplastic syndromes including CRMP-5 optic neuropathies [19].

References