Question

Male cockroaches with mutations that strongly decrease the function of an RTK called RTKX are oblivious to the charms of their female comrades. This particular RTK binds to a small molecule secreted by sexually mature females. Most males carrying loss-of-function mutations in the gene for Ras protein are also unable to respond to females. You have just read a paper in which the authors describe how they have screened cockroaches that are mutant in RTKX for additional mutations that partly restore the ability of males to respond to females. These mutations decrease the function of a protein that the authors call Z. Which of the following types of protein could Z be? Explain your answer.

(a) a protein that activates the Ras protein by causing Ras to exchange GDP for GTP
(b) a protein that stimulates hydrolysis of GTP by the Ras protein
(c) an adaptor protein that mediates the binding of the RTKX to the Ras protein
(d) a transcriptional regulator required for the expression of the Ras gene

Answer 1

Protein Z is likely a protein that enhances the hydrolytic activity of GTP by the Ras protein, which would normally lead to Ras inactivation. A mutation in protein Z reducing its function could leave Ras in an active state longer, thus partly compensating for the RTKX dysfunction in male cockroaches, enabling them to respond to females.

Step-by-step explanation:

If male cockroaches with mutations in an RTK called RTKX are unable to respond to the mating signals from females and additional mutations that partly restore this ability affect the function of a protein called Z, then Z can be conceptualized as being involved in the negative regulation of the RTKX-Ras pathway. Given the options, the most likely type of protein Z could be is (b) a protein that stimulates hydrolysis of GTP by the Ras protein. This hypothesis is based on the understanding that the ability to respond to females was restored; mutations that reduce the function of a negative regulatory element, like a GTPase-activating protein for Ras, would lead to an increased duration of active, GTP-bound Ras and thus could compensate for the reduced function of RTKX.

Normally, the Ras protein alternates between an active state when bound to GTP and an inactive state when bound to GDP. Proteins that enhance the GTPase activity of Ras, such as Z as described in the question, lead to Ras inactivation by accelerating GTP hydrolysis. A mutation that reduces Z's function would limit Ras inactivation, maintaining Ras in a GTP-bound state. In the context of the signaling pathway, this would mean that downstream signals that lead to the male's recognition of females could still be transmitted even with diminished RTKX activity.

Activation of Ras generally triggers the MAP kinase pathway, which can lead to changes in gene expression and cellular behaviors like proliferation. However, when Ras cannot hydrolyze GTP due to inhibitory mutations or because a protein like Z is not functioning properly, it can result in continuous signaling and unregulated cell proliferation, a scenario commonly observed in certain forms of cancer.