You are studying a neurodegenerative disease whose genetic cause maps to a mutat

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You are studying a neurodegenerative disease whose genetic cause maps to a mutation in the p175 gene, which from BLAST searches may belong to the family of 7-transmembrane cell surface receptors. [See scheme of the protein below with each predicted transmembrane segment shown with its most basic flanking region marked.] You quickly generate a polyclonal antibody to human p175, because you want to use Western blotting to show that the disease results from a lack of expression, or perhaps truncation, of the receptor. Unexpectedly though, the Westerns show that patient ("P") and normal ("N") nervous tissue express this protein at comparable levels and that the protein is apparently the same size whether the disease is present or not (see below, left 2 lanes). As a side experiment, you treated the intact, live cells with prior to Western analysis (below, right 2 lanes) This provided the only clue so far that anything was different about p175 in disease-p175 in normal cells was cleaved into several smaller fragments whereas p175 in patient cells was insensitive Schematic of p175 with predicted membrane anchors Western on extracts of patient and normal cell samples Why does the protein product get digested into four discreet products though there are seven membrane anchors? If you inserted an tag at the amino terminus and expressed the protein in cultured cells and did the same experiment, would the labeled species get smaller after treatment, not change, or disappear altogether? Explain what this experiment tells you about the protein in the diseased nerve cells. Assuming that the protein in fact encodes some kind of hormone receptor normally present on the cell surface, what kind of mutation might cause the disease and how would it affect the proteins' function as a receptor? Now suppose you took patient and normal cell extracts from the minus samples and digested them with and without H prior to the Western analysis. What would you expect to see and how would that be consistent with your hypothesis about the disease in A? Is there a precedent for diseases like this?

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