Disease relevance of Syne1

• Passive transfer of reovirus-immune, but not naive, spleen cells prior to infection protected neonatal mice from 8B-induced myocarditis [1].
• In addition, reovirus 8B caused extensive myocarditis in SCID mice [1].
• Prior to infection, passive transfer of monoclonal antibodies specific for 8B capsid proteins protected neonatal mice against 8B-induced myocarditis, indicating that humoral immunity can protect against myocarditis [1].
• The in vivo localising and clearance properties of conjugates of the folate-degrading enzyme carboxypeptidase G2 (CPG2) with anti-human chorionic gonadotrophin (W14A) were measured in nude mice bearing CC3 choriocarcinoma xenografts [2].
• Monoclonal anti-CEA antibody, A5B7, and its fragments conjugated to CPG2 localize to a peak concentration in the LS174T xenografts within 24 h after injection, but enzyme activity persists in plasma such that prodrug injection has to be delayed for 5-6 days in order to avoid toxicity [3].
• Although disruption of neither Syne-1 nor Syne-2 affected viability or fertility, Syne-1; Syne-2 double-knockout mice died of respiratory failure within 20 minutes of birth [4].

High impact information on Syne1

• We have now isolated a third member of the nesprin family that lacks an ABD and instead binds to the plakin family member plectin, which can associate with the intermediate filament (IF) system [5].
• The transgene acted in a dominant interfering fashion, displacing endogenous Syne-1 from the nuclear envelope [6].
• Syne proteins anchor muscle nuclei at the neuromuscular junction [6].
• Syne-1 is concentrated at the nuclear envelope of synaptic nuclei; its Caenorhabditis elegans orthologue ANC-1 functions to tether nuclei to the cytoskeleton [6].
• A reovirus reassortant, 8B, derived from type 1 Lang (T1L) and type 3 Dearing (T3D), displayed a phenotype unlike that of either of its parents in that it efficiently induced numerous macroscopic external cardiac lesions in neonatal mice (B. Sherry, F. J. Schoen, E. Wenske, and B. N. Fields, J. Virol. 63:4840-4849, 1989) [7].

Biological context of Syne1

• The phenylenediamine compounds were found to behave as prodrugs, yielding IC50 prodrug/IC50 drug ratios between 20- and 33-fold (for 37 and 40) and differentials of 12-14-fold between CPG2-expressing and control LacZ-expressing clones [8].
• Tissue distribution studies demonstrated that there was little or no tissue uptake of native CPG2, whereas dextran-CPG2 conjugate, and CNBr-activated dextran were retained in the liver [9].

Anatomical context of Syne1

• A colorectal cell line was engineered to express CPG2 tethered to the outer cell surface [8].

Associations of Syne1 with chemical compounds

• The prodrugs were designed to be activated to their corresponding phenol and aniline nitrogen mustard drugs by CPG2 for use in GDEPT [8].

Analytical, diagnostic and therapeutic context of Syne1

• We have investigated the role of lymphocyte-based immunity in murine myocarditis by using a myocarditic reovirus (reovirus serotype 3 8B), nonmyocarditic reoviruses, adoptive transfer experiments, and mice with severe combined immunodeficiency (SCID mice) [1].
• These results are discussed in relation to the potential use of dextran-CPG2 conjugates in cancer chemotherapy [9].

References