Role of Intermediate Filaments in Vesicular Traffic

Abstract

Intermediate filaments are an important component of the cellular cytoskeleton. The first established role attributed to intermediate filaments was the mechanical support to cells. However, it is now clear that intermediate filaments have many different roles affecting a variety of other biological functions, such as the organization of microtubules and microfilaments, the regulation of nuclear structure and activity, the control of cell cycle and the regulation of signal transduction pathways. Furthermore, a number of intermediate filament proteins have been involved in the acquisition of tumorigenic properties. Over the last years, a strong involvement of intermediate filament proteins in the regulation of several aspects of intracellular trafficking has strongly emerged. Here, we review the functions of intermediate filaments proteins focusing mainly on the recent knowledge gained from the discovery that intermediate filaments associate with key proteins of the vesicular membrane transport machinery. In particular, we analyze the current understanding of the contribution of intermediate filaments to the endocytic pathway.

Keywords: endocytosis; exocytosis; intermediate filaments; intracellular trafficking; membrane traffic; mitosis; vimentin.

Figure 1

Axonal transport of lysosomes in neurons and astrocytes. Neurons and astrocytes communicate with each other. Both the lack of NFL in neurons and of GFAP and vimentin (VIM) in astrocytes affect lysosome mobility.

Figure 2

IFs and vesicle trafficking during cell cycle. Model representing the suggested role of Rab5, Rab21, vimentin filaments and lamins during interphase and mitosis. In interphase, Rab5-positive vesicles can localize also around the nucleus and fusion between these organelles occurs. In metaphase, nuclear lamina disassembly is controlled also by Rab5 and Rab5-positive organelles localize around the spindle poles. At this stage, vimentin filaments are phosphorylated on Ser459 and regulate Rab21 but not Rab5 association with β1-integrin-containing vesicles. Thus, vimentin is associated with endosomes, whose fusion is blocked in metaphase. At later stages lamins are dephosphorylated, the nuclear lamina is assembled and vimentin phosphorylation on Ser459 is required for Rab21-positive β1-integrin vesicles localization at the cleavage furrow where they fuse contributing to separation of daughter cells. Rab5-positive vesicles accumulate around the newly reformed nuclear envelope.