Alternative titles; symbols
HGNC Approved Gene Symbol: LIN7B
Cytogenetic location: 19q13.33 Genomic coordinates (GRCh38): 19:49,114,370-49,118,460 (from NCBI)
By searching EST databases for homologs of C. elegans Lin7, Butz et al. (1998) identified murine Lin7b, which they called Veli2. The deduced 207-amino acid Veli2 protein has a C-terminal PDZ domain. Western blot analysis detected Veli2 in all rat tissues examined, with highest expression in brain.
By Northern blot analysis, Jo et al. (1999) found that rat Lin7b, which they called Mals2, was expressed specifically in brain. Sucrose gradient centrifugation showed enrichment of Mals proteins in rat cerebral cortex synaptosomes. Mals2 had an apparent molecular mass of 25 kD by Western blot analysis.
By immunohistochemistry and in situ hybridization using antibodies and cRNAs specific for mouse Mals1 (LIN7A; 603380), Mals2, and Mals3 (LIN7C; 612332), Misawa et al. (2001) showed that each Mals protein localized to distinct brain regions. The Mals proteins were predominantly expressed in both neuronal cell bodies and neuropil, and they were not detected in most nonneuronal cells in brain.
Using immunohistochemical analysis, Sudo et al. (2006) found that Lin7 proteins colocalized with a tight junction marker at cell-cell contacts in canine kidney cells, in perinuclear and marginal regions and with stress fibers in rat fibroblasts, and throughout the cytoplasm and enriched at the neurite tip in a mouse neuroblastoma cell line.
Butz et al. (1998) identified a complex of 3 proteins in rat brain that had the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. The 3 proteins were Cask (300172), a protein related to membrane-associated guanylate kinases (MAGUKs); Mint1 (APBA1; 602414), a putative vesicular trafficking protein; and the Velis. Cask, Mint1, and the Velis formed a tight, salt-resistant complex. Butz et al. (1998) determined that the N-terminal domains of Cask, Mint1, and the Velis were involved in complex formation, leaving their C-terminal PDZ domains free to recruit adhesion molecules, receptors, and channels to the complex. Butz et al. (1998) proposed that the tripartite complex acts as a nucleation site for the assembly of proteins involved in synaptic vesicle exocytosis and synaptic junctions.
Jo et al. (1999) found that rat Mals proteins immunoprecipitated with Psd95 (DLG4; 602887) and NMDA receptor-2B (NR2B, or GRIN2B; 138252) from solubilized rat cerebral cortex membranes. Protein pull-down assays confirmed the interaction between Mals2, Psd95, and Nr2b and showed that the C-terminal 9 amino acids of Nr2b interacted with the PDZ domain of Mals2. Screening C-terminal peptide sequences revealed that the PDZ domain of MALS2 showed highest affinity for the consensus sequence E(T/S)(R/X)(V/L/I/F), which matches the C terminus of Nr2b.
By yeast 2-hybrid analysis of a human brain cDNA library, Sudo et al. (2006) found that the C terminus of rhotekin (RTKN; 602288) interacted with LIN7B. They confirmed the interaction by protein pull-down assays using recombinant proteins and immunoprecipitation analysis of cotransfected COS-7 cells. A constitutively active version of RHOA (165390), but not activated RAC (602048) or CDC42 (116952), increased the affinity between rhotekin and LIN7B. Lin7 and rhotekin also coimmunoprecipitated from rat brain lysates. Sudo et al. (2006) concluded that LIN7 has a role in neuronal RHO/rhotekin signaling.
Hartz (2008) mapped the LIN7B gene to chromosome 19q13.33 based on an alignment of the LIN7B sequence (GenBank AF311862) with the genomic sequence (build 36.1).
Misawa et al. (2001) obtained Mals1 -/-, Mals2 -/-, and Mals1 -/- Mals2 -/- double-knockout mice at expected mendelian frequencies, and all mutant strains were viable, fertile, and indistinguishable from their wildtype littermates. Electrophysiologic analysis showed normal excitatory synaptic activity in the hippocampal CA1 region of double-knockout animals. However, double-knockout animals showed upregulation of Mals3 in most, but not all, brain regions, suggesting that upregulation of Mals3 may compensate for loss of Mals1 and Mals2 expression.
Butz, S., Okamoto, M., Sudhof, T. C. A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell 94: 773-782, 1998. [PubMed: 9753324] [Full Text: https://doi.org/10.1016/s0092-8674(00)81736-5]
Hartz, P. A. Personal Communication. Baltimore, Md. 9/29/2008.
Jo, K., Derin, R., Li, M., Bredt, D. S. Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex. J. Neurosci. 19: 4189-4199, 1999. [PubMed: 10341223] [Full Text: http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=10341223]
Misawa, H., Kawasaki, Y., Mellor, J., Sweeney, N., Jo, K., Nicoll, R. A., Bredt, D. S. Contrasting localizations of MALS/LIN-7 PDZ proteins in brain and molecular compensation in knockout mice. J. Biol. Chem. 276: 9264-9272, 2001. [PubMed: 11104771] [Full Text: https://doi.org/10.1074/jbc.M009334200]
Sudo, K., Ito, H., Iwamoto, I., Morishita, R., Asano, T., Nagata, K. Identification of a cell polarity-related protein, Lin-7B, as a binding partner for a Rho effector, Rhotekin, and their possible interaction in neurons. Neurosci. Res. 56: 347-355, 2006. [PubMed: 16979770] [Full Text: https://doi.org/10.1016/j.neures.2006.08.003]