Disease relevance of Homer1

• Moreover, AAV-Homer 1a animals showed attenuation of electrographic seizures in a model of status epilepticus [1].
• METHODS: Staining of Vesl-1L/Homer 1c (V-1L) immunoreactivity and TUNEL cytochemistry were used to quantify neuroprotective effects at the synaptic level in a model of mild retinal ischemia induced by temporary middle cerebral artery occlusion in the adult rat [2].
• Elucidation of Homer 1a function in the nucleus accumbens using adenovirus gene transfer technology [3].
• This study suggests that the Homer gene is present in human specimens in the involuting phase of hemangioma, and it might be involved in the growth control [4].

Psychiatry related information on Homer1

• Signaling through group I mGluRs is regulated, in part, by Homer proteins, and it was found that the blunting of group I mGluR-induced glutamate release and motor activity after repeated cocaine was associated with a reduction in Homer1b/c protein that was selective for the medial nucleus accumbens [5].

High impact information on Homer1

• This dynamic transcriptional control suggests that Homer mediates a novel cellular mechanism that regulates metabotropic glutamate signalling [6].
• The Homer gene is also distinct from members of the PDZ family in that its expression is regulated as an immediate early gene and is dynamically responsive to physiological synaptic activity, particularly during cortical development [6].
• Here we report a novel dendritic protein, Homer, that contains a single, PDZ-like domain and binds specifically to the carboxy terminus of phosphoinositide-linked metabotropic glutamate receptors [6].
• PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis [7].
• We demonstrate physiologic binding of PIKE-L to Homer, an adaptor protein known to link metabotropic glutamate receptors to multiple intracellular targets including the inositol 1,4,5-trisphosphate receptor (IP3R) [7].

Biological context of Homer1

• These data suggest that Dyn3 is a postsynaptic dynamin and, like its binding partner Homer, plays a significant role in dendritic spine morphogenesis and remodeling [8].
• Vesl/Homer proteins regulate ryanodine receptor type 2 function and intracellular calcium signaling [9].
• Vesl/Homer proteins have also been implicated in differentiation and physiological adaptation processes [Nat. Neurosci. 4 (2001) 499; Nature 411 (2001) 962; Biochem. Biophys. Res. Commun. 279 (2000) 348] [9].
• K-means cluster analysis revealed two distinct biphasic gene expression patterns that contained 44 genes (including 18 immediate early genes), involved in cell signaling and plasticity (i.e. MAP2K7, Sprouty2, Irs-2, Homer1, GPRC5B, Grasp) [10].
• To determine if the reduction in Homer1b/c may be contributing to cocaine-induced behavioural sensitization, antisense oligonucleotides were infused over two weeks into the nucleus accumbens of rats to reduce Homer1 gene expression by approximately 35% [11].

Anatomical context of Homer1

• (4) Homer1 protein is reduced in the nucleus accumbens, and Homer2 knockout mice show enhanced responsiveness to cocaine [12].
• Here, we demonstrate immunohistochemically that metabotropic glutamate receptor 1alpha (mGluR1alpha) and PSD-Zip45/Homer 1c are colocalized to synapses in the cerebellar molecular layer but not in the hippocampus [13].
• Zif268, Arc and Homer can be modulated in CA1 pyramidal cells approximately twofold after electroshock-induced maximal seizure, which demonstrates potential responsiveness to electrical stimuli [14].
• In granule cells of the dentate gyrus, LTP induced in vivo by tetanic stimulation of the perforant path was followed by strong induction of the immediate early genes (IEGs) Zif268, Arc and Homer [14].
• The PSD-Zip45 is, therefore, the first candidate as receptor anchoring proteins containing leucine zipper motifs in the central nervous system [15].

Associations of Homer1 with chemical compounds

• The postsynaptic scaffold proteins ProSAP1/Shank2 and Homer1 are associated with glutamate receptor complexes at rat retinal synapses [16].
• Actin depolymerization by latrunculin A reduced the synaptic localization of PSD-Zip45, shank, and F-actin but not of PSD-95 or GKAP [17].
• These data indicate that the expression of behavioural sensitization arises in part from a reduction in Homer1 gene products in the accumbens, while the development of sensitization requires stimulation of AMPA/kainate receptors [11].
• Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition [18].
• Here, we present evidence that Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R) [19].

Physical interactions of Homer1

• We have determined the crystal structure of the Homer EVH1 domain complexed with a peptide from mGluR (TPPSPF) [18].

Regulatory relationships of Homer1

• Conversely, a uniform distribution was observed when mGluR5 was expressed alone or with Homer short forms [20].
• Targeted to the PSD by a PDZ-dependent mechanism, Shank promotes the maturation of dendritic spines and the enlargement of spine heads via its ability to recruit Homer to postsynaptic sites [21].
• Sated rats were assessed for food consumption in the presence of a cue that was paired previously with food (CS+), or in the presence of another cue that was never paired with food (CS-), in two consecutive tests temporally arranged for activation of the effector IEGs Arc (activity-regulated cytoskeletal protein) and Homer 1a [22].
• Homer-1 mRNA in the rat suprachiasmatic nucleus is regulated differentially by the retinohypothalamic tract transmitters pituitary adenylate cyclase activating polypeptide and glutamate at time points where light phase-shifts the endogenous rhythm [23].
• Endothelin-1 activates Homer 1alpha expression via mitogen-activated protein kinase in cardiac myocytes [24].

Other interactions of Homer1

• Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer [8].
• Here we report additional members of the Vesl/Homer family of proteins, Vesl-1L and Vesl-2 [25].
• The double-labeling experiments revealed a high rate of colocalization of ProSAP1/Shank2 with Homer1 and PSD-95, and little colocalization with GRIP [16].
• In this study we examined whether the expression and loss of behavioral signs of neuropathic pain were associated with changes in the content of the scaffolding proteins Homer and Shank in the post-synaptic density (PSD) of the spinal dorsal horn [26].
• The EVH1 domain and extreme C-terminal leucine zipper motif of PSD-Zip45 were also critical for these events [17].

Analytical, diagnostic and therapeutic context of Homer1

• Deep brain stimulation in a rat model modulates TH, CaMKIIa and Homer1 gene expression [27].
• Site-directed mutagenesis confirms the importance of specific Homer residues for ligand binding [18].
• Here, the subcellular distribution of recombinant HA1-tagged Homer 1c and HA1-tagged Homer 1a was investigated in C(2)C(12) myotubes and in transgenic skeletal muscle fibers of the adult rat by epifluorescent and confocal microscopy [28].
• By RT-PCR and RNasePA, mRNAs transcripts for Homer 1a and Homer 1c, but not Homer 1b, are detected in both skeletal and cardiac muscles of the rat [29].
• Analysis of HEK-293 cells by PCR showed that they contained mRNA coding for members of the Homer family with the predominant form being Homer-1b, which is consistent with the immunochemical analysis of these cells [30].

References