Disease relevance of DBNL

• We found that HIP-55 knockout mice were viable and fertile but showed decreased body weight and increased occurrence of death within the first 4 weeks after birth [1].
• In these patients, muscle weakness, CMAP amplitudes and motor unit number estimates correlated with clinical disability, while motor NCV did not [2].
• Lower monofilament detection and CMAP were independently associated with lower heel BUA (p < 0.01), and monofilament detection was associated with lower hip BMD (p < 0.05) in regression additionally adjusted for lifestyle factors, bone-active medications, and diabetes-related complications [3].
• CONCLUSIONS: These findings imply that the expression level of CMAP in human cancer may be a new biomarker for both liver metastasis and the patient's outcome [4].
• Thus, we studied the CMAP expression levels using a real-time quantitative reverse transcription-PCR for 79 patients with colorectal cancer, including 17 cases with liver metastasis [4].

High impact information on DBNL

• TCR internalization was slightly increased in HIP-55 knockout T cells [1].
• These phenotypes were accompanied by reduced immune responses, including antigen-specific antibody production and T-cell proliferation in HIP-55 knockout mice [1].
• These results demonstrate the importance of HIP-55 as an adaptor protein in the TCR signaling and immune system [1].
• Consistent with this possibility, SH3P7 colocalizes with actin filaments of the cytoskeleton [5].
• SH3P7 is a cytoskeleton adapter protein and is coupled to signal transduction from lymphocyte antigen receptors [5].

Biological context of DBNL

• To study its function in T cell activation, HIP-55-deficient Jurkat T cells were established using the RNA interference approach [6].
• Cleavage of HIP-55 by caspases dissociated its actin-binding domain from its SH3 domain [7].
• Our findings show that HIP-55 is a key novel component of the immunological synapse that modulates T cell activation by connecting actin cytoskeleton and TCRs to gene activation and endocytic processes [8].
• These results suggest that, in addition to binding to HPK1, HIP-55 might negatively regulate TCR signaling through down-regulation of TCR expression [8].
• Electrophysiology confirmed unaltered NCV, but less reduced CMAP recordings in the treatment group [9].

Anatomical context of DBNL

• HIP-55 binds to actin filaments both in vitro and in vivo [6].
• Dissociation of the SH3 domain from the rest of the HIP-55 protein was observed in the NB4 APL cell line treated with arsenic trioxide due to specific cleavage by caspase 3-like enzymes [10].
• SH3P7 migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a 55-kDa protein that is preferentially expressed in brain, thymus, and spleen [5].
• NCV and CMAP were assessed by surface electroneurography of the right peroneal nerve conducted in 1162 participants, 515 men and 647 women, age 21-96 years, free of major neurological diseases [11].
• Electrophysiological studies revealed a sensory-motor neuropathy, predominantly axonal as evidenced by decreased CMAP amplitudes, with normal distal latencies-velocites, except for median nerve where a prolonged distal latency was observed [12].

Associations of DBNL with chemical compounds

• The main-chain rmsd of the minimum-energy trp-cage conformation obtained for the GB/ACE/CHARMM22/CMAP landscape is less than 1 A. However, this energy function strongly favored helical structures for the two peptides shown by NMR to form beta-sheet structures [13].

Physical interactions of DBNL

• We found that HPK1 bound to HIP-55 both in vitro and in vivo [14].

Enzymatic interactions of DBNL

• ZAP-70 phosphorylated HIP-55 at Tyr-334 and Tyr-344 in vitro and in vivo, and the HIP-55 mutant (Y334F/Y344F) was not tyrosine-phosphorylated in stimulated T cells [6].

Other interactions of DBNL

• The SH3 domain-containing adaptor HIP-55 mediates c-Jun N-terminal kinase activation in T cell receptor signaling [6].
• As controls, the expression of CD28 and the glycosylphosphatidylinositol-linked protein CD59 was not affected by HIP-55 overexpression [8].
• The cleavage of HIP-55 correlated with the induction of PRAM-1 mRNA and protein expression [10].

Analytical, diagnostic and therapeutic context of DBNL

• Lambert-Eaton myasthenic syndrome: A placebo-controlled crossover study reported a significant clinical improvement in the amplitude of the resting CMAP following IVIg treatment [15].
• Distal compound muscle action potential (DCMAP) dispersion, defined as a DCMAP duration >/=9 ms, and proximal-distal (P-D) CMAP dispersion are considered useful in the electrodiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) [16].
• (3) Greater L-PMP-to-CMAP separation in the median than in the ulnar nerve was explained by cadaveric dissection, which revealed that the motor branch (responsible for the trailing CMAP) is longer in the median nerve than in the ulnar nerve relative to each nerve's corresponding digital sensory branch (responsible for the preceding L-PMP) [17].
• The NI is derived from the CMAP, the DML and the F-wave frequency (CMAP amplitude/DML) x F frequency %), representing aspects of the effects of denervation and reinnervation, of degeneration of the terminal part of the motor axons, and of the excitability of anterior horn cells [18].

References