p27kip1 Modulates the Morphology and Phagocytic Activity of Microglia

p27^kip1 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 p27^kip1 function in neural cells, little is known about its relevance in microglia. Here, we studied the role of p27^kip1 in microglia using a combination of in vitro and in situ approaches. While the loss of p27^kip1 did not affect microglial density in the cerebral cortex, it altered their morphological complexity in situ. However, despite the presence of p27^kip1 in microglial processes, as shown by immunofluorescence in cultured cells, loss of p27^kip1 did not change microglial process motility and extension after applying laser-induced brain damage in cortical brain slices. Primary microglia lacking p27^kip1 showed increased phagocytic uptake of synaptosomes, while a cell cycle dead variant negatively affected phagocytosis. These findings indicate that p27^kip1 plays specific roles in microglia.