Figure 2.

Cartoon depicting possible role of shank in shuttling of cytosolic nNOS to the nitrergic nerve terminal membrane. This depicts the basis of the hypothesis of possible role of shank in nitrergic neurotransmission. Different scaffolding proteins are shown with the modular domains without appropriate scale to the full length of the proteins. Details of these modular domains are described in Kim and Sheng (57). nNOS, via interaction with LC8 or PDZ-domain-based interaction, may be shuttled from acto-myosin Va in the cytosol through the actin cortical barrier by shank and GKAP. Shank has multiple protein interaction domains like ankyrin domains, SH3, PDZ, and SAM. Static protein interactions are planned to be examined to test whether such exchanges takes place in enteric nerve terminals. By these mechanisms, shank may play a significant role in nitric oxide synthesis and nitrergic neuromuscular neurotransmission. nNOS–LC8–myosin Va and nNOS–palmitoyl-PSD95 interactions have been demonstrated in enteric nerve terminals (12, 15).