β2SP/TET2 complex regulates gene 5hmC modification after cerebral ischemia

Abstract

Spectrin is the main component of the cytoskeleton and includes α-spectrin (α1, α2) and β-spectrin (β1-5). βII spectrin (β2SP) is encoded by Sptbn1, and it consists of two tandem calponin homology domains (CH1 and CH2), and both contains one actin-binding domain (ABD) in the amino-terminus. 1 β2SP is involved in the regulation of various cell functions, such as proliferation, blood vessel formation and immune response. 2 More recently, β2SP has been linked to multiple signalling pathways, including cell cycle regulation, 3 apoptosis, 4 DNA repair, 5 Wnt signalling, 6 Hippo signalling, 7 Notch signalling, 8 β-catenin signalling 9 and TGFβ signalling. 10 β2SP also has a critical role in the nervous system. Incorrect positioning or deletion of β2SP destroys the cytoskeleton of neuronal dendrites, reduces axons 11,12 and affects the formation of the myelin sheath, which may be related to the mechanism of neuropathy caused by demyelination. 13 As one of the main features of cerebral ischemia, demyelination plays a key role in the mechanism of cerebral ischemia-related injury. Therefore, we believe that β2SP is involved in the mechanism of ischemic injury. There are several reports on the role of α-spectrin in ischemic injury, [14][15][16] but studies of β2SP are lacking.