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.