EHD1 as a Positive Regulator of Macrophage CSF1R

Macrophage biology is regulated via receptor tyrosine kinase (RTK) CSF-1 receptor (CSF1R). Anomalous macrophage biology has been shown to be hallmark in diseases such as cancer and atherosclerosis. Although CSF1R signaling has been studied, little is known about the mechanisms which govern the endocytic trafficking of the receptor. EHD1 is known to regulate endocytic recycling of receptors, but the role of EHD1 in macrophages is unstudied. In this study, we discovered EHD1 knockout (KO) murine bone marrow-derived macrophages (BMDMs) had markedly reduced total and surface CSF1R levels and a corresponding decreased downstream functional output due to decreased CSF1R signaling. EHD1 KO led to perinuclear CSF1R accumulation which co-localized with the Golgi (GM130). These findings reveal a novel and essential role for EHD1 in transporting newly synthesized CSF1R to the cell surface. Our study expands our understanding of RTK trafficking which has potentially dramatic implications for designing new targeted therapies for devastating human diseases.