| 2015 |
C1QL1 (provided by climbing fibers as an anterograde signal) specifically binds to BAI3 (brain-specific angiogenesis inhibitor 3), a cell-adhesion G-protein-coupled receptor expressed on postsynaptic Purkinje cells, and this C1QL1-BAI3 signaling is required to determine and maintain a single-winner climbing fiber in the mouse cerebellum throughout development and adulthood. |
Genetic knockout, binding assays, electrophysiology, immunohistochemistry |
Neuron |
High |
25611509
|
| 2015 |
The C1QL1-BAI3 signaling pathway controls the stereotyped pattern of synaptic connectivity established by excitatory afferents (both climbing fibers and parallel fibers) on cerebellar Purkinje cells; restricted expression of C1QL1 in inferior olivary neurons ensures the proper synaptic territory for climbing fibers. |
Genetic knockout, overexpression, electrophysiology, immunohistochemistry |
Cell reports |
High |
25660030
|
| 2016 |
The globular domain of C1QL1/CTRP14 directly stimulates migration and capillary tube formation of HUVECs in a dose-dependent manner, activating phosphorylation of c-Raf, MEK1/2, ERK1/2, and p90RSK; MEK1/2 inhibition with U0126 blocks these effects. BAI3 immunoreactivity was detected in HUVECs, suggesting BAI3 mediates this proangiogenic effect. |
In vitro angiogenesis assay (HUVEC migration and tube formation), Western blot for phospho-ERK pathway components, pharmacological inhibition (U0126), chick yolk sac membrane assay |
Molecular and cellular biochemistry |
Medium |
27734226
|
| 2009 |
C1QL1 pre-mRNA undergoes A-to-I RNA editing in vivo, causing non-synonymous amino acid substitutions, conserved across human, mouse, and zebrafish; the major editing site had previously been misannotated as a SNP. |
RNA sequencing, comparative genomics, RNA secondary structure analysis |
FEBS letters |
Medium |
19275900
|
| 2023 |
Overexpression of C1ql1 in climbing fibers or Bai3 in Purkinje cells causes transverse CF branches to elongate and form new synapses on distal dendrites of mature Purkinje cells; this reinnervation requires neuronal activity and is dependent on Bai3 in Purkinje cells. Additionally, C1ql1 levels in CFs are upregulated in GluD2 knockout mice, and the reinnervation phenotype of GluD2 KO is absent in Bai3 KO mice, placing C1ql1-Bai3 signaling downstream of GluD2-dependent synapse maintenance. |
Viral overexpression, conditional knockout, electrophysiology, Ca²⁺ imaging, immunohistochemistry, genetic epistasis (GluD2 KO × Bai3 KO double mutant) |
Molecular brain |
High |
37488606
|
| 2021 |
C1ql1 is expressed in outer hair cells of the cochlea in an adolescence-onset, tonotopic gradient pattern. Conditional knockout of C1ql1 in outer hair cells results in histological evidence of reduced outer hair cell afferent synapse maintenance, though auditory behavioral and physiological phenotypes were not compelling. |
Fluorescent reporter knockin mouse, conditional knockout, histology/immunohistochemistry, auditory brainstem response testing |
PloS one |
Medium |
33979385
|
| 2021 |
C1ql1 global knockout mice exhibit progressive hearing loss with reduced auditory nerve fiber innervation of both inner and outer hair cells, and significant outer hair cell loss; however, spiral ganglion neurons are normal ultrastructurally, and IHC presynaptic machinery (synaptic vesicle release, presynaptic proteins) is not significantly affected by C1ql1 deletion. |
Global knockout mouse, auditory brainstem response, DPOAE, confocal microscopy, electron microscopy, voltage-clamp recording, immunocytochemistry |
Frontiers in cellular neuroscience |
High |
34512267
|
| 2022 |
C1QL1 deficiency in mice (via intraperitoneal and intrabursal injection of C1QL1 antiserum) impairs folliculogenesis, reduces granulosa cell autophagy, alleviates C1QL1-mediated inhibition of granulosa cell apoptosis, elevates circulating estradiol, reduces hypothalamic KISS1 and GnRH expression, and decreases serum FSH, leading to depletion of ovarian follicle reserve. |
Antibody-mediated blockade (IP + intrabursal injection), immunohistochemistry, ELISA for hormones, confocal microscopy for follicle staging |
Endocrinology |
Medium |
35560215
|
| 2022 |
CTRP14/C1QL1 deficiency in mice alters physical activity and food intake in a sex- and nutritional state-dependent manner (lower activity in fed males, increased activity in fasted/refed females, reduced food intake in refed males), but is largely dispensable for metabolic homeostasis, body composition, and insulin sensitivity. |
Constitutive knockout mouse, metabolic cage analysis (physical activity, food intake), body composition analysis, glucose tolerance test, insulin tolerance test, lipid profiling |
American journal of physiology. Endocrinology and metabolism |
Medium |
35403439
|
| 2024 |
C1QL1 is expressed in oligodendrocyte progenitor cells (OPCs) and its deficiency (OPC-specific conditional KO) reduces OPC differentiation into oligodendrocytes and myelin production during development and after cuprizone-induced demyelination; conversely, in vivo overexpression of C1QL1 increases oligodendrocyte density and myelination during recovery. C1QL1 levels bidirectionally regulate OPC differentiation in primary culture. |
OPC-specific conditional knockout, in vivo viral overexpression, cuprizone demyelination model, primary OPC culture, immunohistochemistry |
The FEBS journal |
High |
39257292
|
| 2025 |
The trimeric globular C1q (gC1q) domain of C1ql1 undergoes calcium-modulated domain-swapping to form a hexamer; cryo-EM reveals calcium ions stabilize the C1ql1_gC1q hexamer in complex with the extended CUB domain of BAI3. Full-length C1ql1 further assembles into linear clusters via the gC1q hexamer, providing a scaffold to accumulate BAI3 receptors on the plasma membrane, supporting synapse maintenance. |
Cryo-EM structure determination, biochemical assembly assays, computational analysis, cellular and in vivo functional validation |
Nature communications |
High |
41372137
|
| 2025 |
C1QL1 interacts with BAI3 in the cochlea (confirmed by colocalization and co-immunoprecipitation), and regulates auditory nerve fiber growth via the BAI3-ELMO1-DOCK180-RAC1 pathway; C1ql1 overexpression inhibits expression of the TIAM1-PARD3 pathway. |
Co-immunoprecipitation, colocalization imaging, overexpression/knockdown with pathway component analysis |
Acta oto-laryngologica |
Medium |
40193629
|
| 2025 |
In breast cancer, C1QL1 localizes to the endoplasmic reticulum and interacts with HSP90α and VCP (confirmed by co-immunoprecipitation and mass spectrometry), facilitating their ubiquitin-mediated degradation and thereby inducing ER stress/unfolded protein response (ERS/UPR) and caspase-dependent apoptosis. C1QL1 promoter methylation silences its expression in breast cancer. |
LC-MS/MS, co-immunoprecipitation, Western blot, overexpression/knockdown in vitro and in vivo (nude mice), flow cytometry (apoptosis/cell cycle), TUNEL, methylation-specific PCR |
Experimental & molecular medicine |
Medium |
40583061
|
| 2026 |
Glioblastoma-secreted C1QL1 binds to BAI3 on neighboring neurons and GBM cells, activating RAC1-mediated cytoskeleton rearrangement to prune normal synapses and promote tumor microtube (TM) outgrowth and malignant synapse formation; a non-GEF-targeting RAC1 inhibitor rescues C1QL1-mediated synaptic pruning and inhibits glioma recurrence. |
In vitro signaling assays, pharmacological inhibition (RAC1 inhibitor), in vivo glioma models, functional rescue experiments |
Cancer discovery |
Medium |
41747254
|