Protruding membrane nanotubes: attachment of tubular protrusions to adjacent cells by several anchoring junctions

Abstract

Membrane nanotubes are a morphologically versatile group of membrane structures (some resembling filopodia), usually connecting two closely positioned cells. In this article, we set morphological criteria that distinguish the membrane nanotubes from filopodia, as there is no specific molecular marker known to date that unequivocally differentiates between filopodia and protruding nanotubes. Membrane nanotubes have been extensively studied from the morphological point of view and the transport that can be conducted through them, but little is known about the way they connect to the adjacent cell. Our results show that the nanotubes may connect to a neighboring cell by anchoring junctions. Among cell adhesion proteins, N-cadherin, β-catenin, nectin-2, afadin and the desmosomal protein desmoplakin-2 were immune-labeled. We found that N-cadherin and β-catenin are concentrated in nanotubes, while the concentrations of other junction-involved proteins are not increased in these structures. On the basis of data from transmission electron microscopy, we propose a model of the nanotube attachment where the connection of nanotubes is stabilized by several anchoring junctions, most likely adherens junctions that are formed when the nanotube is sliding along the target cell membrane.