Kinesin‐1 (uKHC/KIF5B) is Required for Bidirectional Motility of ER Exit Sites and Efficient ER‐to‐Golgi Transport

Gupta, Vijay; Palmer, Krysten J.; Spence, Peter; Hudson, Andrew J.; Stephens, David

doi:10.1111/j.1600-0854.2008.00811.x

Cited by 48 publications

(51 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, it seems that dynein plays a role in ERGIC positioning. Similar results were recently obtained for COPII-coated ER exit sites (41), supporting the idea that this mechanism may operate along the secretory pathway.…”

Section: Discussionsupporting

confidence: 89%

Regulation of ER-Golgi Intermediate Compartment Tubulation and Mobility by COPI Coats, Motor Proteins and Microtubules

Tomàs

Martínez‐Alonso

Ballesta

et al. 2010

Traffic

View full text Add to dashboard Cite

Little is known about the formation and regulation of endoplasmic reticulum (ER)-Golgi transport intermediates, although previous studies suggest that cargo is the main regulator of their morphology. In this study, we analyze the role of coat protein I (COPI) and cytoskeleton in the formation of tubular ER-Golgi intermediate compartment (ERGIC) and also show that partial COPI detachment by means of low temperature (15 • C) or brefeldin A induces the formation of transient tubular ERGIC elements. Most of them moved from the cell periphery to the perinuclear area and were 2.5× slower than vesicles. Time-lapse analysis of living cells demonstrates that the ERGIC elements are able to shift very fast from tubular to vesicular forms and vice versa, suggesting that the amount of cargo is not the determining factor for ERGIC morphology. Both the partial microtubule depolymerization and the inhibition of uncoating of the membranes result in the formation of long tubules that grow from round ERGICs and form at complex network. Interestingly, both COPI detachment and microtubule depolymerization induce a redistribution of kinesin from peripheral ERGIC elements to the Golgi area, while dynein distribution is not affected. However, both kinesin and dynein downregulation by RNA interference induced ERGIC tubulation. The tubules induced by kinesin depletion were static, whereas those resulting from dynein depletion were highly mobile. Our results strongly suggest that the interaction of motor proteins with COPI-coated membranes and microtubules is a key regulator of ERGIC morphology and mobility.

show abstract

Section: Discussionsupporting

confidence: 89%

Regulation of ER-Golgi Intermediate Compartment Tubulation and Mobility by COPI Coats, Motor Proteins and Microtubules

Tomàs

Martínez‐Alonso

Ballesta

et al. 2010

Traffic

View full text Add to dashboard Cite

show abstract

“…For many cargos, interference with their plus-or minusdirected motor protein completely disrupts their movement, suggesting a strong link between dynein and kinesin. Bidirectional movements have been described previously for ERES (ER exit sites) and were proved to be driven by microtubule-associated motor proteins [32]. Whether bidirectional movements are due to a motor co-ordination or a tug-of-war between opposing motors is still hotly discussed and probably depends on the system under investigation [33,34].…”

Section: The Importance Of Bidirectional Transportmentioning

confidence: 96%

The role of motor proteins in endosomal sorting

Hunt

Stephens

2011

Biochemical Society Transactions

View full text Add to dashboard Cite

Microtubule motor proteins play key roles in the spatial organization of intracellular organelles as well as the transfer of material between them. This is well illustrated both by the vectorial transfer of biosynthetic cargo from the endoplasmic reticulum to the Golgi apparatus as well as the sorting of secretory and endocytic cargo in the endosomal system. Roles have been described for dynein and kinesin motors in each of these steps. Cytoplasmic dynein is a highly complex motor comprising multiple subunits that provide functional specialization. The family of human kinesins includes over 40 members. This complexity provides immense functional diversity, yet little is known of the specific requirements and functions of individual motors during discrete membrane trafficking steps. In the present paper, we describe some of the latest findings in this area that seek to define the mechanisms of recruitment and control of activity of microtubule motors in spatial organization and cargo trafficking through the endosomal network.

show abstract

“…Cells were either transfected with a duplex RNA oligonucleotide that targets the ubiquitous kinesin-1 heavy chain DNA in positions 2973-2991 downstream of the open reading frame (sense, 5Ј-AUGCAUCUCGUGA-UCGCAA-dTdT-3Ј; antisense, 3Ј-dTdTUACGUAGAGCA-CUAGCGUU-5Ј) or transfected with a combination of two other double strand RNAs against KHC (38). In the first case, transfections were performed twice using HiPerfect reagent (Qiagen) according to the manufacturer's instructions with an RNA concentration of 5 nmol/liter at days 0 and 4.…”

Section: Methodsmentioning

confidence: 99%

Starvation-induced Hyperacetylation of Tubulin Is Required for the Stimulation of Autophagy by Nutrient Deprivation

Geeraert

Ratier

Pfisterer

et al. 2010

Journal of Biological Chemistry

171

201

View full text Add to dashboard Cite

The molecular mechanisms underlying microtubule participation in autophagy are not known. In this study, we show that starvation-induced autophagosome formation requires the most dynamic microtubule subset. Upon nutrient deprivation, labile microtubules specifically recruit markers of autophagosome formation like class III-phosphatidylinositol kinase, WIPI-1, the Atg12-Atg5 conjugate, and LC3-I, whereas mature autophagosomes may bind to stable microtubules. We further found that upon nutrient deprivation, tubulin acetylation increases both in labile and stable microtubules and is required to allow autophagy stimulation. Tubulin hyperacetylation on lysine 40 enhances kinesin-1 and JIP-1 recruitment on microtubules and allows JNK phosphorylation and activation. JNK, in turn, triggers the release of Beclin 1 from Bcl-2-Beclin 1 complexes and its recruitment on microtubules where it may initiate autophagosome formation. Finally, although kinesin-1 functions to carry autophagosomes in basal conditions, it is not involved in motoring autophagosomes after nutrient deprivation. Our results show that the dynamics of microtubules and tubulin post-translational modifications play a major role in the regulation of starvation-induced autophagy.Macroautophagy (simply referred to here as autophagy) occurs at low basal levels to perform homeostatic functions such as protein and organelle turnover. It is also an adaptive catabolic response to different metabolic stresses, including nutrient deprivation, growth factor depletion, or hypoxia (1, 2). Newly assembled multilayer membranes expand and sequester parts of the cytoplasm to form autophagosomes that subsequently fuse with lysosomes to degrade their content (1, 2). When cells lack nutrients, inhibition of the mammalian target of rapamycin activates the ULK complex (ULK1 and ULK2 are the mammalian orthologs of the yeast Atg1) to initiate the cascade of events leading to the formation of autophagosomes (reviewed in Ref.3). Building of isolation membranes or phagophores involves a complex comprising Beclin 1 (Beclin 1 is the mammalian homolog of the yeast Atg6) and the class III PI3K 4 (PI3K(III), also called hVps34) (4). Newly synthesized phosphatidylinositol 3-phosphate then recruits effectors such as WIPI-1, the homolog of yeast Atg18 (5, 6), to allow the recruitment of other autophagosomal building bricks (4). Atg9 contributes to membrane shuttling that elongates the pre-autophagosomal membrane (reviewed in Ref. 7). Such elongation also involves ubiquitin-like machineries, which in turn allow Atg12-to-Atg5 conjugation, and the modification of LC3 (LC3 is the mammalian ortholog of the yeast Atg8) (8) prior to their recruitment to autophagosomal membranes. LC3 is a light chain of MAP1 first identified in neurons (9, 10). After autophagy induction, the C-terminal region of native LC3 (pro-LC3) is cleaved by Atg4, yielding LC3-I. Atg7 and Atg3 then conjugate LC3-I to phosphatidylethanolamine on its C-terminal glycine, yielding LC3-II that attaches to the autophagosomal membrane ...

show abstract

Kinesin‐1 (uKHC/KIF5B) is Required for Bidirectional Motility of ER Exit Sites and Efficient ER‐to‐Golgi Transport

Cited by 48 publications

References 61 publications

Regulation of ER-Golgi Intermediate Compartment Tubulation and Mobility by COPI Coats, Motor Proteins and Microtubules

Regulation of ER-Golgi Intermediate Compartment Tubulation and Mobility by COPI Coats, Motor Proteins and Microtubules

The role of motor proteins in endosomal sorting

Starvation-induced Hyperacetylation of Tubulin Is Required for the Stimulation of Autophagy by Nutrient Deprivation

Contact Info

Product

Resources

About