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

ABSTRACT

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.