Biochemical and Biophysical Research Communications
FLRT3, a cell surface molecule containing LRR repeats and a FNIII domain, promotes neurite outgrowth☆
Section snippets
Materials and methods
All procedures involving animals were reviewed and approved by the local Institutional Animal Care and Use Committee.
Construction of the FLRT3 expression vectors. All expression vectors were constructed using the GATEWAY system (Invitrogen). We constructed two destination vectors, pcDNA5FRT/Igκleader/HA/ccdB and pcDNA/ccdB/HA. An oligonucleotide coding for the HA tag, and a GATEWAY Reading Frame Cassette B, fragment were sequentially ligated into the KpnI–EcoRV sites of the pSecTag2/C vector
FLRT3 is localized in the plasma membrane
Previously, we performed a comprehensive analysis of gene expression following injury in the distal stump of the axotomized sciatic nerve using cDNA microarrays [7]. An EST clone, AI227034, was found to be induced 3.9-fold 7 days after axotomy, and was selected for further study. Induction of the gene expression was confirmed by RT-PCR in the previous study. AI227034 had significant overlap with the RIKEN cDNA, AK017456, which has a putative open reading frame. This protein coded by the clone
Discussion
Upon axotomy, Schwann cells in the distal nerve segment undergo extensive changes along with axonal degeneration. Myelin sheaths are dissoluted and subsequently absorbed by the surrounding cellular environment, a process called Wallerian degeneration. During dissolution and absorption of myelin sheaths by macrophages, the remaining Schwann cells divide and align longitudinally within basal lamina tubes while extending slender cytoplasmic processes, which form the cellular strands called the
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Cited by (51)
Feedback regulation of RTK signaling in development
2019, Developmental BiologyCitation Excerpt :In chick, flrt3 is necessary but not sufficient for proper formation of the limb organizer called the apical epidermal ridge (AER) and co-localized with fgf8 expression and Erk activity (Tomas et al., 2011). Flrt3 knockout mice are embryonic lethal due to fusion defects and impaired definitive endoderm migration, phenotypes attributed to FLRT3's function as a cell-adhesion molecule (Egea et al., 2008; Karaulanov et al., 2006; Maretto et al., 2008; Tsuji et al., 2004). X. laevis biochemical analyses in vivo and in vitro revealed that FLRT proteins complex with FGFRs to promote downstream signaling of the MAPK/ERK pathway via their intracellular domain (Fig. 1B) (Bottcher et al., 2004).
Role of LRRTMs in synapse development and plasticity
2017, Neuroscience ResearchRegulation of FGF signaling: Recent insights from studying positive and negative modulators
2016, Seminars in Cell and Developmental BiologyCitation Excerpt :The intracellular domain is characterized by a short cytoplasmic tail (illustrated in Fig. 1B). FLRT3 was localized to the cell surface of cultured neurons or transfected CHO cells [136–138]. The focus of many studies in the context of FGF signaling has been on FLRT3 owing to the discovery that in frogs FGF8-XFLRT3 constitute a positive feedback loop whereby FGF8 mRNA injection induces XFLRT3 expression and, in turn, XFLRT enhances FGF signaling through activating the ERK/MAPK pathway and inducing the mesodermal marker Xbra [51].
Axon guidance: FLRTing promotes attraction
2014, Current BiologyCitation Excerpt :Leyva-Diaz et al. [4] noted that FLRT3 was a particularly intriguing candidate to examine in the context of Netrin-1 signaling in rTCAs. Not only is FLRT3 known to regulate neurite outgrowth [9,10], it was recently shown to bind the Netrin receptor Unc5 [11], which plays a role in caudal TCA guidance [12]. The authors discovered that FLRT3 was expressed in a decreasing rostral-to-caudal gradient in developing thalamic neurons; hence, it was enriched specifically in rTCAs.
Latrophilins function as heterophilic cell-adhesion molecules by binding to teneurins: Regulation by alternative splicing
2014, Journal of Biological ChemistryCitation Excerpt :However, mRNAs for Lphn1 and its ligand Ten2 remained constant compared with WT littermates (Fig 10B). Quite surprisingly, mRNA levels for Lphn3 and its ligand FLRT3 were both up-regulated, denoting that elevated gene expression was induced for this pair of adhesion molecules following neurodegenerative signals, a mechanism reminiscent of neuronal response to nerve injury regarding FLRT3 mRNA (Fig. 10C) (25–27). Lphn3 and FLRT3 are part of a specific array of cell-adhesion molecule mRNAs that were found to be up-regulated, including neuroligin-1, SynCAM, dystroglycan, and N-cadherin, which might constitute a signature for CSPα KΟ-induced neurodegeneration.
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Abbreviations: EST, expressed sequence tag; N-CAM, neural cell adhesion molecule; FNIII, fibronectin type III.