Disease relevance of RTN3

• The differential expression of hRTN3 between astrocytoma and non-cancerous tissue may provide insight into the progress of astrocytoma [1].

High impact information on RTN3

• In brain, BACE1 mainly colocalizes with RTN3 in neurons, whereas RTN4 is more enriched in oligodendrocytes [2].
• Our previous study demonstrated that the overexpression of reticulon 3 (RTN3, also named HAP, homologue of ASY protein) caused apoptosis with the depletion of ER Ca(2+) stores [3].
• These results supported that the release of ER Ca(2+) stores triggered the initial signal-transducing pathways for EOR induced by overexpressed RTN3 [3].
• Our studies showed that overexpressed RTN3 induced EOR, eliciting ER-specific apoptosis with activation of caspase-12 and mitochondrial dysfunction through ER Ca(2+) depletion and the sustained elevation of cytosolic Ca(2+) [3].
• ER Ca2+ depletion triggers apoptotic signals for endoplasmic reticulum (ER) overload response induced by overexpressed reticulon 3 (RTN3/HAP) [3].

Biological context of RTN3

• In the present paper, we describe the existence of five new isoforms of RTN3 that differ in their N-termini, and analysed their tissue distribution and expression in neurons [4].
• Specifically, RTN3A1 expression was down-regulated upon cell death of cerebellar granule neurons triggered by potassium deprivation [4].
• We redefined the structure of human and murine rtn3 genes, and identified two supplementary exons that may generate up to seven putative isoforms arising by alternative splicing or differential promoter usage [4].
• In cells where RTN3 displayed a filamentous/reticular distribution, protein transport between the ER and Golgi was blocked, and Golgi proteins were dispersed [5].
• Although RTN3 can form homo- or heterodimers in cells, BACE1 mainly binds to the RTN monomer and disruption of the QID triplet does not interfere with the dimerization [6].

Anatomical context of RTN3

• Northern blotting hybridization revealed higher expression of hRTN3 in normal brain and some endocrine-related organs such as thyroid relative to other non-endocrine organs [1].
• RTN1 and RTN3 belong to the reticulon (RTN) gene family, which are primarily expressed in the endoplasmic reticulum [7].
• ER-bound RTN3 protein recruited endogenous FADD to the ER membrane and subsequently initiated caspase-8 cascade, including activation of caspase-8, processing of Bid and release of cytochrome c from mitochondria [8].
• Characterization of the ASYIP gene may be very useful in clarifying the mechanism of ASY-induced apoptosis or Nogo-involved inhibition of neuronal regeneration in the central nervous system [9].
• In situ hybridization with a mouse RTN3-A1-specific cRNA probe revealed that the mouse RTN3-A1 mRNA was regionally expressed in the neurons of the cerebral cortex, hippocampus, hypothalamus, and cerebellum of the adult mouse brain [10].

Associations of RTN3 with chemical compounds

• Furthermore, we demonstrated that endogenous FADD was recruited by ER-bound endogenous RTN3 to the ER membrane under the tunicamycin stimulation [8].
• The ASYIP protein contains two hydrophobic regions and a double lysine endoplasmic reticulum (ER) retrieval motif at its C-terminus, which was shown to be identical to RTN3, a reticulon family protein of unknown function [9].

Physical interactions of RTN3

• Here, we focused our study on RTN3 and further show that a C-terminal QID triplet conserved among mammalian RTN members is required for the binding of RTN to BACE1 [6].
• Subtle changes in RTN3 membrane topology can disrupt its binding to BACE1 and its inhibitory effects on BACE1 activity [11].

Co-localisations of RTN3

• By immunofluorescence analysis, the ASYIP protein was shown to be co-localized with ASY in the ER [9].

Other interactions of RTN3

• Cloning of a novel member of the reticulon gene family (RTN3): gene structure and chromosomal localization to 11q13 [12].

Analytical, diagnostic and therapeutic context of RTN3

• To investigate the mechanism of ASY-induced apoptosis or inhibition of neuronal regeneration, we cloned a cDNA for the ASY-interacting protein from the human cDNA library using the yeast two-hybrid method, and obtained a cDNA we designated as ASYIP [9].
• With Western blot analysis, the expected 100-kDa RTN3-A1 protein was detected in mouse brain [10].

References