Neurofibromin interacts with the cytoplasmic Dynein Heavy Chain 1 in melanosomes of human melanocytes

•We identify a novel interaction between NF1 and DHC in melanocytes.•We demonstrate that NF1 and DHC interact along microtubules.•We demonstrate that NF1 and DHC colocalize with melanosomes.•We propose that the NF1-DHC interaction is relevant in melanosome localization. Neurofibromin (NF1) is encoded by the NF1 tumour suppressor gene. Mutations result in a disorder known as Neurofibromatosis Type 1 (NF-1), and patients are often diagnosed due to the presence of unusual pigmentary patterns that include Café au lait macules (CALMs). Little is known about how loss of NF1 results in pigmentary defects in melanocytes. We sought to identify novel NF1 interacting proteins and elucidate the molecular mechanisms underlying the pigmentary defects. The cytoplasmic Dynein Heavy Chain 1 (DHC) was found to interact with NF1 along microtubules in vesicular structures identified to be melanosomes. Our studies suggest that NF1 is involved in melanosomal localization, and that disruptions in NF1–DHC interactions may contribute to the abnormal pigmentary features commonly associated with this debilitating syndrome. NF1physically interacts with DHC by anti bait coimmunoprecipitation (View interaction)