title: 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.
authors.affiliation: The Arthur and Sonia Labatt Brain Tumour Research Centre, Toronto, Canada; Cell Biology Program, Hospital for Sick Children, Toronto, Canada. vedant.arun@utoronto.ca
authors.forename: Vedant
authors.initials: V
authors.lastname: Arun
authors.forename: Lionel
authors.initials: L
authors.lastname: Worrell
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wiley
authors.forename: David R
authors.initials: DR
authors.lastname: Kaplan
authors.forename: Abhijit
authors.initials: A
authors.lastname: Guha
mesh_terms: D002478:Cells, Cultured; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D020460:Melanosomes / Q000187:drug effects / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D025542:Neurofibromin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D014018:Tissue Distribution / Q000187:drug effects / Q000235:genetics
chemical_list: C511240:DYNC1H1 protein, human; D025542:Neurofibromin 1; D034741:RNA, Small Interfering; D056445:Cytoplasmic Dyneins