Homer protein family regulation in skeletal muscle and neuromuscular adaptation

Abstract

Scaffolding adaptor proteins of the Homer family have recently been implicated in regulation of a large number of physiological processes owing to their remarkable ability to coordinate a complex network of different molecular players within the same signaling pathway. However, because of their unique molecular properties that also allow functional modulation of a plethora of different interacting protein partners, Homers seem to play additional and important roles in the integration of several molecular players belonging to different signaling pathways and thus allowing crosstalk. The role of the Homer protein family has been previously extensively investigated in neuronal tissue where it was first discovered as a new protein family being upregulated in response to brain seizures (Brakeman P.R., et al., Nature 1997, 386, 284-288.). Recently, the role of Homers was also proposed in skeletal muscle physiology. For instance, it has been shown that Homers regulate both the myogenic differentiation program and the open probability (Po) of several ion channels. Furthermore, by knocking out Homer1, one of the three Homer genes, mice carrying such deletion displayed a pronounced skeletal muscle myopathy associated with altered transient receptor potential activity and calcium homeostasis. Homer expression has now been further characterized at the neuromuscular junction in skeletal muscle. Apart from their known role at central synapses, Homers are important physiological determinants in differentiation, development, and adaptation in skeletal muscle and the neuromuscular system and thus integrating motor neuron control, for example, with downstream calcium signaling pathways in muscle fibers. V C 2013 IUBMB Life, 65(9): [769][770][771][772][773][774][775][776] 2013

Integrative Analysis of Genomics and Transcriptome Data to Identify Potential Functional Genes of BMDs in Females

“…The gene HOMER1 , located on 5q14.2, binds group 1 metabotropic glutamate receptors (mGluRs) . Although the relationship between Homer family members and glutamate receptors has not been reported in bone tissue in cell biology studies, HOMER1 is naturally associated with glutamate receptors signaling in many other tissues such as brain, peripheral neuronal tissue and skeletal muscle tissue . Based on this background and our integrative analysis results, we speculated that HOMER1 plays an important role in glutamate signaling, which is thought to be important in bone remodeling, especially in bone resorption.…”

Identification of Homer1 as a Potential Prognostic Marker for Intrahepatic Cholangiocarcinoma

“…During the decade Homer system but also exist in various peripheral tissues, including cardiac and skeletal muscles (Xiao et al, 1998;Sandona et al, 2000). Apart from their known role at central synapses, Homers are important physiological determinants in differentiation, development, and adaptation in skeletal muscle and the neuromuscular system, and thus integrating motor neuron control, for example, with downstream calcium signaling pathways in muscle fibers (Salanova et al, 2013). Homer1 expressed differentially between benign and malignant pheochromocytomas.The differentially expressed with known function belonged to 8 biologic process categories: plays important functions in the biology of ICC and shows a more aggressive tumor phenotype of ICC.…”

Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration

“…Moreover, Dnmt3a expression is activated by neuronal activity, and partially through the nuclear calcium signaling-dependent pathway (30). In the case of skeletal muscles, calcium ions enter the muscle cells during muscle contraction, which is caused by motor neuron stimulation (31). Stimulation of motor neurons may be important for maintaining Dnmt3a expression in skeletal muscles.…”