Neuropilin 1 (NRP1) plays an important but ill-defined role in VEGF-A signaling and vascular morphogenesis. We show that mice with a knockin mutation that ablates the NRP1 cytoplasmic tail (Nrp1(cyto)) have normal angiogenesis but impaired developmental and adult arteriogenesis. The arteriogenic defect was traced to the absence of a PDZ-dependent interaction between NRP1 and VEGF receptor 2 (VEGFR2) complex and synectin, which delayed trafficking of endocytosed VEGFR2 from Rab5+ to EAA1+ endosomes. This led to increased PTPN1 (PTP1b)-mediated dephosphorylation of VEGFR2 at Y(1175), the site involved in activating ERK signaling. The Nrp1(cyto) mutation also impaired endothelial tubulogenesis in vitro, which could be rescued by expressing full-length NRP1 or constitutively active ERK. These results demonstrate that the NRP1 cytoplasmic domain promotes VEGFR2 trafficking in a PDZ-dependent manner to regulate arteriogenic ERK signaling and establish a role for NRP1 in VEGF-A signaling during vascular morphogenesis.
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http://dx.doi.org/10.1016/j.devcel.2013.03.019 | DOI Listing |
Neuropathology
January 2025
Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Embryonal tumors with multilayered rosettes (ETMRs) are rare and highly aggressive embryonal central nervous system tumors that predominantly affect infants younger than 3 years old. These tumors typically have a C19MC alteration (ETMR, C19MC-altered) or, more rarely, a DICER1 mutation (ETMR, DICER1-mutated). Post-chemotherapeutic or post-chemoradiotherapeutic histological changes of C19MC-altered ETMRs, such as maturation or loss of histological characteristics of ETMR have been described in several reports.
View Article and Find Full Text PDFStructure
January 2025
Department of Chemistry, Britannia House, 7 Trinity Street, King's College London, London, SE1 1DB, UK; School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK. Electronic address:
Tripartite resistance nodulation and cell division multidrug efflux pumps span the periplasm and are major drivers of multidrug resistance among gram-negative bacteria. Cations, such as Mg, become concentrated within the periplasm and, in contrast to the cytoplasm, its pH is sensitive to conditions outside the cell. Here, we reveal an interplay between Mg and pH in modulating the structural dynamics of the periplasmic adapter protein, AcrA, and its function within the prototypical AcrAB-TolC multidrug pump from Escherichia coli.
View Article and Find Full Text PDFEcotoxicol Environ Saf
January 2025
Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China; Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, PR China. Electronic address:
Arsenic in the environment, such as sodium arsenic (NaAsO), is a frequently occurring hazard that has been linked to nonalcoholic steatohepatitis (NASH). Our prior research established the involvement of ferroptosis in arsenic-induced NASH, but the precise underlying mechanisms remain elusive. Here, we found that exposure to NaAsO had a suppressive effect on the expression of CDGSH iron-sulfur domain-containing protein 2 (CISD2) at the protein and gene levels, and overexpression of CISD2 inhibited NaAsO-induced ferroptosis and NASH.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA.
Complexins are a family of small presynaptic proteins that regulate neurotransmitter release at nerve terminals and are highly conserved in evolution. While direct interactions with SNARE proteins are critical for all complexin functions, binding of their disordered C-terminal domains (CTD) to membranes, especially to synaptic vesicle membranes, is essential for the ability of complexin to inhibit vesicle release. Furthermore, while some complexin CTDs possess an endogenous affinity for membranes, other complexin isoforms are subject to lipidation at their C-termini, which is presumed to confer additional membrane binding.
View Article and Find Full Text PDFNat Commun
January 2025
Molecular Genetics of Eukaryotes, University of Kaiserslautern, Kaiserslautern, Germany.
Molecular chaperones are essential throughout a protein's life and act already during protein synthesis. Bacteria and chloroplasts of plant cells share the ribosome-associated chaperone trigger factor (Tig1 in plastids), facilitating maturation of emerging nascent polypeptides. While typical trigger factor chaperones employ three domains for their task, the here described truncated form, Tig2, contains just the ribosome binding domain.
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