Материал из hpluswiki
Перейти к навигации Перейти к поиску

DCC-interacting protein 13-beta (Dip13-beta) (Adapter protein containing PH domain, PTB domain and leucine zipper motif 2) [DIP13B]


The reversal effect of physical exercise on aging-related increases in APPL2 content in skeletal muscle.

The aim of this study was to evaluate the effects of aging on intracellular adiponectin signaling and the possible therapeutic effect of physical exercise. Fischer 344 rats were distributed in the following groups: Young (3 months old); Sedentary Old (Old, 27 months old); and Old Exercised (Old-Exe, 27 months old), which were subjected to a short-term exercise training protocol. The results showed that the old rats presented glucose intolerance without increased adiposity. However, short-term exercise training reversed this disorder, which was associated with a decrease in the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif (APPL) isoform 2 (APPL2) content. The APPL isoform 1 (APPL1) and TRB3 (Tribbles homolog 3) contents were not altered. Akt phosphorylation was only increased in the old exercised rats. There was a reduction in the content of adiponectin receptor 1 in the old rats. The short-term exercise training protocol was able to decrease APPL2 content in the skeletal muscle, which was accompanied by an improvement in the glucose tolerance of the old Fischer 344 rats. These findings provide new evidence supporting the role of physical exercise as a non-pharmacological therapeutic intervention to attenuate age-related deficits.

MeSH Terms

  • Adaptor Proteins, Signal Transducing
  • Aging
  • Animals
  • Glucose Intolerance
  • Muscle, Skeletal
  • Nerve Tissue Proteins
  • Physical Conditioning, Animal
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Rats, Inbred F344


  • APPL1
  • APPL2
  • Aging
  • Insulin
  • Physical exercise
  • Skeletal muscle

Adaptor Protein APPL2 Affects Adult Antidepressant Behaviors and Hippocampal Neurogenesis via Regulating the Sensitivity of Glucocorticoid Receptor.

Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins involved in regulating many biological activities and processes. The newly identified metabolic factor APPL2 showed the potentials to modulate cell growth, but whether APPL2 could affect adult neurogenesis and animal mood behaviors remains unknown. In the present study, APPL2 transgenic (Tg) mice and wild-type littermates were used for testing our hypothesis that APPL2 could affect glucocorticoid receptor (GR) signaling and modulate hippocampal neurogenesis, which contributes to depressive and anxiety behaviors. Compared with WT littermates, APPL2 Tg mice had enhanced GR phosphorylation under basic condition but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. APPL2 Tg mice had decreased hippocampal neurogenesis that was reversed by GR antagonist RU486. APPL2 Tg mice also showed the impaired hippocampal neurogenesis and presented the depressive and anxiety behaviors. In conclusion, APPL2 could be an important regulator for adult neurogenesis. APPL2 overexpression could blunt the activation of glucocorticoid receptor when undergoing environmental stress. Our study suggests that APPL2 might be a new therapeutic target for mental disorders.

MeSH Terms

  • Adaptor Proteins, Signal Transducing
  • Aging
  • Animals
  • Antidepressive Agents
  • Anxiety
  • Behavior, Animal
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Depression
  • Hippocampus
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • Neurogenesis
  • Neurons
  • Phosphorylation
  • Receptors, Glucocorticoid
  • Retinal Ganglion Cells
  • Signal Transduction
  • Stress, Physiological


  • APPL2
  • Adult neurogenesis
  • Behavior
  • Depression
  • Glucocorticoid receptor
  • Hippocampus