Disease relevance of LRRC7

• Latency-associated promoter 1 (LAP1) of herpes simplex virus type 1 is required to generate a series of latency-associated transcripts (LATs) in sensory neurons of latently infected animals [1].

High impact information on LRRC7

• The sequence of densin-180 contains 17 leucine-rich repeats, a sialomucin domain, an apparent transmembrane domain, and a PDZ domain [2].
• Immunocytochemical localization of densin-180 in dissociated hippocampal neuronal cultures shows that the protein is highly concentrated at synapses along dendrites [2].
• The message encoding densin-180 is brain specific and is more abundant in forebrain than in cerebellum [2].
• We propose that densin-180 participates in specific adhesion between presynaptic and postsynaptic membranes at glutamatergic synapses [2].
• We present a detailed comparative analysis of the PDZ domains of the human LAP proteins Erbin, Densin-180, and Scribble and the MAGUK ZO-1 [3].

Biological context of LRRC7

• Densin-180, a protein purified from the postsynaptic density fraction of the rat forebrain, is the founding member of a newly described family of proteins termed the LAP (leucine-rich repeats and PSD-95/Dlg-A/ZO-1 (PDZ) domains) family that plays essential roles in establishment of cell polarity [4].
• Although Densin-180 was reported to be a transmembrane protein, Densin-180 was not accessible to surface biotinylation in dissociated hippocampal neurons; hence Densin-180 may be a cytosolic protein [4].
• We have cloned a novel splice variant of densin-180 from a fetal brain cDNA library and termed it LRRC7 [5].
• In contrast, phosphorylation of densin-180 by CaMKII at serine-1397 only slightly decreases its affinity for CaMKII [6].
• We demonstrate by yeast two-hybrid and biochemical assays that the intracellular portion of densin-180, the alpha-subunit of CaMKII (CaMKIIalpha), and alpha-actinin interact with each other at distinct binding sites and can form a ternary complex stabilized by multiple interactions [6].

Anatomical context of LRRC7

• The specific interaction of densin-180 with holoenzymes of CaMKII containing only alpha-subunit and the increased affinity of CaMKII for densin-180 after autophosphorylation suggest that densin-180 may be involved in localization of activated CaMKII synthesized in dendrites [6].
• The N-terminal leucine-rich repeat region, which is not involved in binding shank, targets Densin-180 to the plasma membrane in transfected cells and to the basolateral membrane of epithelial cells [7].

Associations of LRRC7 with chemical compounds

• The soybean (Glycine max (L.) Merrill) seed leucine aminopeptidase locus (Lap1) was found to be linked to the Kunitz trypsin inhibitor locus (Ti) with a recombination frequency of 15.3 percent +/- 0.9 percent [8].

Physical interactions of LRRC7

• Densin-180 PDZ domain binds the COOH terminus of delta-catenin/NPRAP containing the PDZ domain-binding sequence [4].
• Here we report the identification of the alpha-subunit of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and alpha-actinin-4 as potential binding partners for the densin-180 intracellular segment [6].

Other interactions of LRRC7

• Coexpression of shank3 abrogates branch formation and targets Densin-180 into postsynaptic clusters instead [7].
• Leucine-rich repeat and PDZ [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] domain proteins such as scribble and Densin-180 have been implicated in the establishment of cell-cell contacts [7].
• In mammals, three LAP proteins have been described, Densin-180, Erbin, and hScribble [9].

Analytical, diagnostic and therapeutic context of LRRC7

• Sequence analysis and DNA binding studies have suggested the existence of several cis-acting elements within LAP1 that are potentially important for promoter function, although their role in LAT gene expression during latency is largely unexplored [1].
• A reduction in LAT synthesis measured by in situ hybridization and reverse transcription-PCR (RT-PCR) of rat brain tissue latently infected with a LAP1 TATA substitution virus demonstrated that this sequence was required for full LAP1 activity in vivo [1].

References