Fig. 6: Molecular architecture model of the neuronal MPS in the neurite-neurite fasciculations.

In neurites, actin filaments form ring-like structures that are connected by spectrin tetramers, and actin filaments in these rings are likely capped by adducin and tropomodulin at their fast- and slow-growing ends, respectively. The length and structure of the actin filaments within the actin rings remains an open question and a recent electron microscopy study suggested the possibility that actin rings in the AIS are made of long, intertwined actin filaments²⁹. Dematin and coronin bind to the actin filaments, and ankyrin B and ankyrin G bind to the site near the center of each spectrin tetramer. The NMII bipolar filaments bind preferentially to actin filaments within the same actin rings and may regulate the diameter of neurites by exerting radial contractile forces. It is possible that a smaller fraction of NMII bipolar filaments may connect adjacent actin rings. Membrane proteins, such as ion channels, cell adhesion molecules, receptors and signaling molecules, are associated either with the actin filaments through adaptor proteins such as dematin, or with the center positions of spectrin tetramers through adaptor proteins such as ankyrin. Recruitment of cell adhesion molecules to periodic sites on the MPS and interactions of cell adhesion molecules between two abutting neurites bring their respective MPS structures in phase, which could in turn bring additional MPS-bound cell adhesion molecules from the two neurites into proximity, enhancing neurite-neurite interactions. Moreover, the MPS could serve as a structural platform that organizes transmembrane proteins and membrane-associated signaling molecules, potentially facilitating a variety of signaling pathways in neurons.