Fig. 1

The molecular mechanism of SYNPO2 nuclear-cytoplasmic shuttling. The upper part depicts six different isoforms of SYNPO2 including their motifs, domains and signaling sequences, while the lower part shows the process of nuclear-cytoplasmic shuttling of SYNPO2, which typically involves four stages: (1) the 14-3-3 beta binding sites (BS) on SYNPO2 are phosphorylated by PKA or CaMKII; (2) after phosphorylation of SYNPO2, Importin α and β interact with the nuclear localization sequence of SYNPO2; (3) importin α and β lead SYNPO2 shuttling from cytoplasm to nucleus. (4) If many phosphatases such as λ-PPase and CnA are activated, dephosphorylation of SYNPO2 induces binding with mAKAP and α-actinin to keep its retention in the cytoplasm