| 1995 |
SEZ-6 encodes a brain-specific type I transmembrane protein containing five short consensus repeats (SCRs/sushi domains, complement C3b/C4b binding sites) and two CUB domain-like sequences, plus a signal sequence, threonine-rich domain, transmembrane domain, and short cytoplasmic tail. The protein is post-translationally modified and expressed in cerebrum and cerebellum. |
cDNA cloning, sequence analysis, in vitro translation, immunoblot with anti-SEZ6 peptide antibody |
Brain research. Molecular brain research / Biochemical and biophysical research communications |
High |
7488116 7723619
|
| 1995 |
SEZ-6 exists in at least three isoforms generated by alternative splicing: one encoding a membrane protein with the full complement of SCRs/CUB domains, one encoding a membrane protein with a different C-terminal region, and one encoding a secreted protein with two SCRs and one CUB-like domain. |
PCR-based cDNA cloning and sequence analysis |
Biochemical and biophysical research communications |
Medium |
7488116
|
| 2007 |
Sez-6 is required for normal dendritic arborization of cortical pyramidal neurons: sez-6 null mice exhibit excess short dendrites and excessive neurite branching in cultured cortical neurons. Membrane-bound and secreted Sez-6 isoforms exert opposing effects on dendritic branching, with membrane-bound Sez-6 exerting an anti-branching effect under basal and depolarizing conditions. Loss of Sez-6 also reduces dendritic spine density and PSD-95 punctate staining, and reduces excitatory postsynaptic responses in layer V pyramidal neurons. |
Sez-6 null mouse analysis, isoform overexpression rescue in knockout neurons, slice electrophysiology, immunostaining for PSD-95 |
Neuron |
High |
18031681
|
| 2021 |
Sez6 family members (Sez6, Sez6L, Sez6L2) inhibit complement activation: they inhibit C3b/iC3b opsonization by classical and alternative pathways. Using Sez6L2 as representative, the mechanism involves (1) accelerating dissociation of C3 convertases (decay-accelerating activity) and (2) functioning as a cofactor for Factor I to facilitate cleavage of C3b (but not C4b). Sez6 is the strongest classical pathway inhibitor among family members. |
In vitro complement opsonization assay, C3 convertase decay assay, Factor I cofactor assay with purified proteins |
Frontiers in immunology |
High |
33936031
|
| 2015 |
N-glycosylation of Sez-6 regulates its cell surface distribution and function. Sez-6 has 11 N-glycosylation sites in three clusters (SC1-3, SC4-7, SC8-11) in the extracellular domain. Mutants lacking the SC4-7 cluster fail to induce filopodia-like protrusions, indicating SC4-7 is required for this activity. The unglycosylated mutant and mutants with only one cluster showed altered localization on the cell membrane compared to wild-type even distribution. |
Site-directed mutagenesis of N-glycosylation sites, transfection into Neuro2a cells, immunofluorescence, conditioned medium analysis |
Biochemical and biophysical research communications |
Medium |
25960298
|
| 2011 |
Sez-6 promotes neurite outgrowth in PC12 cells: shRNA-mediated knockdown of Sez-6 inhibited NGF-induced neurite outgrowth and was associated with increased PKCγ protein levels, suggesting Sez-6 acts through the PKCγ signaling pathway. |
shRNA knockdown in PC12 cells, NGF treatment, neurite outgrowth measurement, PKCγ Western blot |
Zeitschrift fur Naturforschung. C, Journal of biosciences |
Low |
22351987
|
| 2018 |
BACE1 cleaves Sez6 and Sez6L, shedding their extracellular domains. Enhanced BACE1 cleavage of Sez6 and Sez6L is detected in NPC1-null mouse brains at 4 weeks of age. In NPC1-null primary cortical neurons, Sez6 and Sez6L show increased punctate staining within the endolysosomal pathway, suggesting trafficking defects within the endolysosomal pathway contribute to enhanced BACE1 proteolysis. |
Immunoblot quantification of BACE1-cleaved fragments in NPC1-/- vs wild-type mouse brains, immunofluorescence of endolysosomal markers in primary neurons |
PloS one |
Medium |
29979789
|
| 2019 |
The type I transmembrane isoform of Sez6 is cleaved by BACE1, resulting in shedding of the Sez6 extracellular domain; BACE1-shed Sez6 is detectable in human cerebrospinal fluid by Western blot. |
Western blot detection of shed Sez6 ectodomain in human CSF samples |
Pain reports |
Medium |
31041421
|
| 2020 |
Triple knockout of all three Sez6 family proteins (Sez6, Sez6L, Sez6L2) reduces dendritic spine density in the hippocampus and shifts spine morphology toward more immature forms in the somatosensory cortex, establishing a collective role for the Sez6 family in dendritic spine structure. |
Sez6 triple knockout mice, dendritic spine morphology analysis (imaging) |
Cerebral cortex |
Medium |
31711114
|
| 2022 |
In the 5xFAD Alzheimer's disease mouse model, accumulation of BACE1 around amyloid plaques does NOT result in enhanced proteolysis of Sez6 or Sez6L (in contrast to APP). Instead, Sez6 and Sez6L show altered spatial distribution in peri-plaque regions, suggesting their localization but not their BACE1-mediated cleavage is affected in AD pathology. |
Immunoblot for BACE1-cleaved Sez6/Sez6L fragments in 5xFAD vs wild-type brains, immunofluorescence co-localization |
Mechanisms of ageing and development |
Medium |
35998821
|
| 2022 |
Alternative splicing of Sez6 produces isoforms with distinct brain region-specific expression patterns; convulsant drug stimulation increases expression of recessive (secreted) isoforms alongside the dominant transmembrane isoform in cultured cortical neurons, indicating neuronal activity modulates isoform balance. |
Isoform-specific qPCR on mouse brain area punches and cultured cortical neurons treated with convulsant |
Biochemical and biophysical research communications |
Low |
36368155
|