Interaction of early secretory pathway and Golgi membranes with microtubules and microtubule motors

Abstract

This review summarizes the data describing the role of cellular microtubules in transportation of membrane vesicles - transport containers for secreted proteins or lipids. Most events of early vesicular transport in animal cells (from the endoplasmic reticulum to the Golgi apparatus and in the opposite recycling direction) are mediated by microtubules and microtubule motor proteins. Data on the role of dynein and kinesin in early vesicle transport remain controversial, probably because of the differentiated role of these proteins in the movements of vesicles or membrane tubules with various cargos and at different stages of secretion and retrograde transport. Microtubules and dynein motor protein are essential for maintaining a compact structure of the Golgi apparatus; moreover, there is a set of proteins that are essential for Golgi compactness. Dispersion of ribbon-like Golgi often occurs under physiological conditions in interphase cells. Golgi is localized in the leading part of crawling cultured fibroblasts, which also depends on microtubules and dynein. The Golgi apparatus creates its own system of microtubules by attracting γ-tubulin and some microtubule-associated proteins to membranes. Molecular mechanisms of binding microtubule-associated and motor proteins to membranes are very diverse, suggesting the possibility of regulation of Golgi interaction with microtubules during cell differentiation. To illustrate some statements, we present our own data showing that the cluster of vesicles induced by expression of constitutively active GTPase Sar1a[H79G] in cells is dispersed throughout the cell after microtubule disruption. Movement of vesicles in cells containing the intermediate compartment protein ERGIC53/LMANI was inhibited by inhibiting dynein. Inhibiting protein kinase LOSK/SLK prevented orientation of Golgi to the leading part of crawling cells, but the activity of dynein was not inhibited according to data on the movement of ERGIC53/LMANI-marked vesicles.

Elimination of fukutin reveals cellular and molecular pathomechanisms in muscular dystrophy-associated heart failure

“…Golgi-derived MT networks serve important roles in post-Golgi trafficking, maintenance of Golgi integrity, cell polarity, and cellular function 42 . The disruption of MT dynamics in Fktn -deficient myocytes may impact Golgi vesiculation, with the accumulation and densification of MTs affecting both the central cellular localization of Golgi and ER–Golgi–plasma membrane trafficking, which indirectly impacts the size and morphology of the Golgi 58 . Recent studies show that disintegration of Golgi structure and function is one of the main causes of Alzheimer’s disease 42 .…”

Cytoskeleton Aberrations in Alkaptonuric Chondrocytes

“…The whole complex is physically connected to the cytoskeleton and its function and structure is strictly related to the cytoskeletal organization. Vesicles produced by the Golgi apparatus are driven within the cytoplasm through an active mechanism of transport, mediated by actin and microtubule filaments (Fokin et al, ). Therefore, general observations have shown that microtubule depolymerization causes Golgi fragmentation while actin depolymerization causes Golgi compaction (Valderrama et al, ; Thyberg and Moskalewski, ).…”

Golgi fragmentation in Alzheimer's disease

“…One possibility is through the disruption of the microtubule network by tau precipitation and NFT formation (Liazoghli et al, 2005 ). Microtubule defects may affect both the central localization of the Golgi in the cell and ER-Golgi-plasma membrane trafficking that indirectly impacts the size and morphology of the Golgi (Fokin et al, 2014 ). Tau could also affect vesicle trafficking by inhibiting the binding of motor proteins such as kinesins to microtubules (Seitz et al, 2002 ).…”