RTN1-A/NSP: Proteins and Enzymes

Reticulon-1 (RTN1) is a multi-pass membrane protein that is a member of a family of conserved proteins that are primarily located in the endoplasmic reticulum (ER) and play a role in promoting membrane curvature. Reticulons (RTN1-4) share a conserved reticulon homology domain in their C-terminus, which is important for the localization of RTNs in the ER as they do not contain the canonical N-terminal ER-localization signal. Alternative splicing of the human gene generates two major isoforms, RTN1-A and RTN1-C, and, to a lesser extent, a third variant termed RTN1-B.

The canonical isoform, RTN1-A, also known as Neuroendocrine-specific Protein (NSP), is 776 amino acids (aa) in length with a predicted molecular weight of approximately 135 kDa. RTN1-C lacks aa 1-568 and contains a 20 aa substitution for aa 569-588. RTN1-B lacks aa 1-420. Human RTN1-A/NSP shares 82% aa sequence identity with the rat ortholog.

RTN1 is widely expressed in neurons in the developing and mature brain, as well as in neuroendocrine tissue. It is suggested to play a role in neuronal differentiation and DNA binding/epigenetic modifications. RTN1-A/NSP has been shown to form a stable association with the ryanodine receptor RyR2 and modify RyR2-mediated calcium signaling. Research has also shown that RTN1-A/NSP may also function as a potential growth cone marker in elongating neurons.