PMID- 24573299 OWN - NLM STAT- MEDLINE DCOM- 20140422 LR - 20211021 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 34 IP - 9 DP - 2014 Feb 26 TI - SPIG1 negatively regulates BDNF maturation. PG - 3429-42 LID - 10.1523/JNEUROSCI.1597-13.2014 [doi] AB - We previously identified SPARC-related protein-containing immunoglobulin domains 1 (SPIG1, also known as Follistatin-like protein 4) as one of the dorsal-retina-specific molecules expressed in the developing chick retina. We here demonstrated that the knockdown of SPIG1 in the retinal ganglion cells (RGCs) of developing chick embryos induced the robust ectopic branching of dorsal RGC axons and failed to form a tight terminal zone at the proper position on the tectum. The knockdown of SPIG1 in RGCs also led to enhanced axon branching in vitro. However, this was canceled by the addition of a neutralizing antibody against brain-derived neurotrophic factor (BDNF) to the culture medium. SPIG1 and BDNF were colocalized in vesicle-like structures in cells. SPIG1 bound with the proform of BDNF (proBDNF) but very weakly with mature BDNF in vitro. The expression and secretion of mature BDNF were significantly decreased when SPIG1 was exogenously expressed with BDNF in HEK293T or PC12 cells. The amount of mature BDNF proteins as well as the tyrosine phosphorylation level of the BDNF receptor, tropomyosin-related kinase B (TrkB), in the hippocampus were significantly higher in SPIG1-knockout mice than in wild-type mice. Here the spine density of CA1 pyramidal neurons was consistently increased. Together, these results suggest that SPIG1 negatively regulated BDNF maturation by binding to proBDNF, thereby suppressing axonal branching and spine formation. FAU - Suzuki, Ryoko AU - Suzuki R AD - Division of Molecular Neurobiology, National Institute for Basic Biology, and School of Life Science, Graduate University for Advanced Studies, Okazaki, Aichi 444-8787, Japan. FAU - Matsumoto, Masahito AU - Matsumoto M FAU - Fujikawa, Akihiro AU - Fujikawa A FAU - Kato, Akira AU - Kato A FAU - Kuboyama, Kazuya AU - Kuboyama K FAU - Yonehara, Keisuke AU - Yonehara K FAU - Shintani, Takafumi AU - Shintani T FAU - Sakuta, Hiraki AU - Sakuta H FAU - Noda, Masaharu AU - Noda M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Amino Acids) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcium-Binding Proteins) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Sparcl1 protein, mouse) RN - 0 (dolaisoleucine) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Amino Acids/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Calcium-Binding Proteins/genetics/*metabolism MH - Cells, Cultured MH - Chick Embryo MH - Extracellular Matrix Proteins/genetics/*metabolism MH - Gene Expression Regulation, Developmental/genetics/*physiology MH - Green Fluorescent Proteins/genetics MH - Hippocampus/cytology MH - Humans MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Protein Binding/genetics MH - Rats MH - Retina/cytology/embryology/growth & development MH - Retinal Ganglion Cells/*metabolism/ultrastructure MH - Signal Transduction/genetics MH - Synapses/genetics/metabolism/ultrastructure PMC - PMC6795298 OTO - NOTNLM OT - BDNF OT - BDNF maturation OT - SPIG OT - axon branching OT - follistatin-like protein OT - spine formation EDAT- 2014/02/28 06:00 MHDA- 2014/04/23 06:00 PMCR- 2014/08/26 CRDT- 2014/02/28 06:00 PHST- 2014/02/28 06:00 [entrez] PHST- 2014/02/28 06:00 [pubmed] PHST- 2014/04/23 06:00 [medline] PHST- 2014/08/26 00:00 [pmc-release] AID - 34/9/3429 [pii] AID - 1597-13 [pii] AID - 10.1523/JNEUROSCI.1597-13.2014 [doi] PST - ppublish SO - J Neurosci. 2014 Feb 26;34(9):3429-42. doi: 10.1523/JNEUROSCI.1597-13.2014.