Expression profile of the STAND protein Nwd1 in the developing and mature mouse central nervous system

• Published in: Journal of comparative neurology (1911) Vol. 526; no. 13; pp. 2099 - 2114
• Main Authors: Yamada, Seiya, Sakakibara, Shin‐ichi
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.09.2018; Wiley Subscription Services, Inc
• Subjects: Animals; Animals, Newborn; Apaf1; Apoptosis; Apoptotic Protease-Activating Factor 1 - biosynthesis; Apoptotic Protease-Activating Factor 1 - genetics; Axonal plasticity; Blood vessels; Cell death; Cellular stress response; Central nervous system; Central Nervous System - embryology; Central Nervous System - growth & development; Central Nervous System - metabolism; Cytochrome c; Embryos; Environmental effects; Immune response; Immunohistochemistry; Innate immunity; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Male; Mice; Mice, Inbred ICR; Mitosis; Mitosis - genetics; Nervous system; Nestin; Neural stem cells; Neural Stem Cells - metabolism; neuron; Nwd1; Oligomerization; Peptidase; Plasticity (neural); Progenitor cells; Proteins; RRID: AB_10598496; RRID: AB_2161024; RRID: AB_2313564; RRID: AB_2314691; RRID: AB_2314882; RRID: AB_2716798; RRID: AB_477010; Signal transduction; signal transduction ATPases with numerous domains; STAND; Tissue Distribution; Transduction; RRID: AB_10598496; RRID: AB_477010; neuron; RRID: AB_2314691; STAND; central nervous system; Nwd1; RRID: AB_2716798; Apaf1; RRID: AB_2313564; RRID: AB_2314882; signal transduction ATPases with numerous domains; RRID: AB_2161024
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24495

The orchestrated events required during brain development, as well as the maintenance of adult neuronal plasticity, highly depend on the accurate responses of neuronal cells to various cellular stress or environmental stimuli. Recent studies have defined a previously unrecognized, broad class of multidomain proteins, designated as signal transduction ATPases with numerous domains (STAND), which comprises a large number of proteins, including the apoptotic peptidase activating factor 1 (Apaf1) and nucleotide‐binding oligomerization domain‐like receptors (NLRs), central players in cell death and innate immune responses, respectively. Although the involvement of STANDs in the central nervous system (CNS) has been postulated in terms of neuronal development and function, it remains largely unclear. Here, we identified Nwd1 (NACHT and WD repeat domain‐containing protein 1), as a novel STAND protein, expressed in neural stem/progenitor cells (NSPCs). Structurally, Nwd1 was most analogous to the apoptosis regulator Apaf1, also involved in mitosis and axonal outgrowth regulation in the CNS. Using a specific antibody, we show that, during the embryonic and postnatal period, Nwd1 is expressed in nestin‐positive NSPCs in vivo and in vitro, while postnatally it is found in terminally differentiated neurons and blood vessels. At the subcellular level, we demonstrate that Nwd1 is preferentially located in the cytosolic compartment of cultured NSPCs, partially overlapping with cytochrome c. These observations imply that Nwd1 might be involved in the neuronal lineage as a new STAND gene, including having a pro‐apoptotic or nonapoptotic role, similar to Apaf1. We identified Nwd1 as a novel STAND family member expressed in neural stem/progenitor cells, and revealed the detailed expression pattern in the mouse nervous system. As Nwd1 is structurally and phylogenetically most analogous to Apaf1, it might play a pro‐apoptotic or nonapoptotic role in the neuronal lineage, similar to Apaf1.