8.A.47.1.5
Neuropilin-1, NRP1, of 923 aas and 2 TMSs, N- and C-terminal. NRP1 localizes to mitochondria and interacts with the mitochondrial transporter, ABCB8 (TC# 3.A.1.201.22). NRP1 loss reduces ABCB8 levels, resulting in iron accumulation, iron-induced mitochondrial superoxide production, and iron-dependent EC senescence. The region of this protein that is homologous to other members of the Neuropilin (Neto) family are residues 26 to 245. Then there is a repeat sequence of about 120 residues, from 278 to 424 and repeated in residues 436 to 583. Residues 601 to the end show similarity to Meprin A (TC#8.A.77.2.1). NRP1 regulates mitochondrial iron transport via interaction with ABCB8/MITOSUR (Issitt et al. 2019). Neuropilin-1 mediates SARS-CoV-2 infection of astrocytes in brain organoids, inducing inflammation leading to dysfunction and death of neurons (Kong et al. 2022). Angiotensin converting enzyme 2 (ACE-2), transmembrane serine protease 2 (TMPRSS-2) and Neuropilin-1 cellular receptors support the entry of SARS-CoV-2 into susceptible human target cells including astrocytes in the blood brain barrier (BBB) (Malik et al. 2023). Neuropilin-1 interacts with VE-cadherin and TGFBR2 to stabilize adherens junctions and prevent activation of an endothelium under flow; it more generally stabilizes protein complexes at cell-cell junctions while supression endothelial inflamation (Bosseboeuf et al. 2023). Neuropilin-1 is essential for vascular endothelial growth factor A-mediated increase of sensory neuron activity and development of pain-like behaviors (Gomez et al. 2023).  Neuropilin 1 promotes unilateral ureteral obstruction-induced renal fibrosis via RACK1 in Renal tubular epithelial cells (Hou and Du 2023).