Pathology Hiding in Plain Sight: The NF1 Plasma Membrane.
The passive voice and the active voice: for example, is it a matter of “at” or “to?” The NF1 gene product, neurofibromin, in its interaction with the oncoprotein, Ras, does something to the cell’s
plasma membrane; the reactions in question do not merely happen at the cell’s
PM. Moreover, what the Nfn does to the PM in NF1 cells has been seriously underestimated
because of yet another perspective issue.
. The vast majority of publications on the membrane-bound interaction of Nfn and Ras have been
been from the perspective that, first and foremost if not exclusively the NF1 gene is considered a “tumor suppressor gene.” This is rather narrow, respecting the ancient origin and very highly conserved nature of the NF1 alphabetical code, and the intuitive understanding that the vast majority of eukaryotic species are not at risk for tumors or cancer.
However, with the advent and ready availability of genomic analyses now being exploited to understand the nature of normal and abnormal primitive organisms, such as amoebae, Nfn
has been identified as a very important contributor to ordinary cell biology, particularly as relates to nutrition and feeding. Fortunately, with the basic science work from the United Kingdom and southern California and elsewhere, a more realistic picture of the NF1 supergene3 is coming to light. Bloomfield et al1 and Zhang et al2 have made it unequivocally clear that both the wildtype and mutant alleles at the NF1 locus in amoeba – Dictyostelium
specifically – do something to the organism’s anatomic engagement with the rest of the world, that is, it’s PM. Whether and how
the organism lives depends on what its NF1 gene does to its PM. This is a far cry from the NF1 gene being exclusively a safeguard
against cancer.