Inscuteable spindle orientation adaptor protein (INSC)

Inscuteable spindle orientation adaptor protein (INSC) is an adaptor protein that plays a crucial role in regulating spindle orientation during asymmetric cell division, especially in stem cells and progenitor cells. INSC functions by bridging cell polarity complexes (notably the Par complex with Par3/Par6/aPKC) and the spindle orientation machinery (including LGN and Gαi in mammals, Pins in Drosophila), ensuring proper alignment of the mitotic spindle along the polarity axis of dividing cells[1][2][3]. This alignment allows for asymmetric segregation of fate determinants, influencing daughter cell differentiation and tissue organization[1][3][4]. INSC localizes apically and interacts with polarity protein Bazooka (Par3 in mammals) and spindle orientation proteins. Structural studies demonstrate that INSC competitively binds LGN, displacing NuMA (or Mud in Drosophila), which modulates the generation of spindle pulling forces and attachment to the cell cortex[1][3]. While its misregulation may impact stem cell fate and tissue architecture, there are no direct therapeutic targeting strategies or drugs known for INSC at present, and its primary recognized role is as a highly conserved molecular regulator of spindle orientation, not as a conventional pharmacological target[1][2][3][4].

Other names

Protein inscuteable homologInscinscuteable spindle orientation adaptor proteinprotein inscuteable homologinscuteable homolog