How endocytic adaptor AP-2 maintains Purkinje cell function and movement

In neurodegenerative movement disorders, cerebellar Purkinje cells are lost but the mechanisms remain unclear.

The researchers show that endocytic adaptor protein complex 2 (AP-2) is crucial for Purkinje cell survival. They demonstrate that AP-2 interacts and stabilizes the parallel fibers (PFs)-enriched protein  GRID2IP to regulate synaptic function in Purkinje cells.

Loss of AP-2 disrupts synaptic connectivity, alters network activity, and impacts motor coordination. Mechanistically loss of AP-2 triggers GRID2IP degradation and glutamate δ2 receptor (GLURδ2) accumulation, leading to an excess of PFs while climbing fibers (CFs) are reduced.

This study highlights the importance of AP-2 in cerebellar function and its implications for neurodegenerative disorders.

https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00027-0

https://sciencemission.com/AP-2-maintains-Purkinje-cell-function