p27kip1 Modulates the Morphology and Phagocytic Activity of Microglia

Abstract

p27kip1 is a multifunctional protein that promotes cell cycle exit by blocking the activity of cyclin/cyclin-dependent kinase complexes as well as migration and motility via signaling pathways that converge on the actin and microtubule cytoskeleton. Despite the broad characterization of p27kip1 function in neural cells, little is known about its relevance in microglia. Here, we studied the role of p27kip1 in microglia using a combination of in vitro and in situ approaches. While the loss of p27kip1 did not affect microglial density in the cerebral cortex, it altered their morphological complexity in situ. However, despite the presence of p27kip1 in microglial processes, as shown by immunofluorescence in cultured cells, loss of p27kip1 did not change microglial process motility and extension after applying laser-induced brain damage in cortical brain slices. Primary microglia lacking p27kip1 showed increased phagocytic uptake of synaptosomes, while a cell cycle dead variant negatively affected phagocytosis. These findings indicate that p27kip1 plays specific roles in microglia.

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“…To measure phagocytosis of synaptosomes, a phagocytosis assay was performed as previously described with some modifications (Beeken et al, 2022). Briefly, synaptosomes were harvested from Wildtype hiPSC-derived neurons using Syn-PER Synaptic Protein Extraction Reagent (# 87793; Thermo Fisher Scientific).…”