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. Author manuscript; available in PMC: 2016 May 1.
Published in final edited form as: Inflamm Bowel Dis. 2016 May;22(5):1137–1150. doi: 10.1097/MIB.0000000000000750

Figure 2. Normal and mutated NOD2 functions.

Figure 2

A. Normal functions of NOD2. The normal NOD2 variant is activated by muramyl dipeptide, which is a component of bacterial cell walls. Activated NOD2 recruits receptor-interacting protein 2 (PIP2), which then activates the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NFκB) cascades. This results in the release of proinflammatory molecules to help kill pathogenic bacteria (Left). Activated NOD2 also guides autophagy-related 16-like 1 (ATG16L1) protein from the cytoplasm to the plasma membrane to initiate autophagosome formation (Right).

B. Mutated variants of NOD2 cause impairments in sensing and recognizing MDP. Without this activation, RIP2 and the resulting cytokine release does not occur (Left). Without active NOD2, ATG16L1 is not guided to the plasma membrane and remains in the cytosol, which impairs autophagosome formation and results in impaired killing of invading bacteria (Right). NOD2 variants and their impaired cellular functions may lead to dysbiosis within the intestinal epithelium, and are associated with earlier onset of ileal Crohn’s disease.