Asymmetric CLASP-Dependent Nucleation of Noncentrosomal Microtubules at the trans-Golgi Network

Ефимов, А С; Kharitonov, Alexey; Efimova, Nadia; Lončarek, Jadranka; Miller, Paul M.; Andreyeva, Natalia; Gleeson, Paul; Galjart, Niels; Maia, Alexandra S.; McLeod, Ian X.; Yates, John R.; Maiato, Hélder; Khodjakov, Alexey; Akhmanova, Anna; Kaverina, Irina

doi:10.1016/j.devcel.2007.04.002

Cited by 442 publications

(623 citation statements)

References 40 publications

(48 reference statements)

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“…7). These results indicate that MTCL1 plays essential roles in the stable growing of MTs from the Golgi membrane, as has been demonstrated for CLASPs and AKAP450/ CG-NAP 8,9 .…”

supporting

confidence: 76%

“…5b). Previous studies have shown that the CLASPs complex preferentially localizes to the trans-Golgi region 8 , whereas the AKAP450/CG-NAP complex localizes to the cis-Golgi region 9 . Immunofluorescent staining of MTCL1 showed many overlaps not only with the signals of the CLASPs complex, but also with those of the AKAP450/CG-NAP complex (which was identified by an anti-GM130 antibody, because of lack of an appropriate antibody for double staining; Fig.…”

mentioning

confidence: 95%

“…Taken together, these studies have provided not only new insight into the importance of MTs in organelle architecture, but also evidence for the physiological significance of this vertebrate-specific Golgi architecture. However, in spite of the significant achievements of these studies, the detailed molecular mechanisms underlying the MT nucleation from the Golgi membrane remain to be clarified, although the involvement of g-tubulin has been demonstrated 8 . In addition, it is unclear how the perinuclear subpopulation of MTs corresponding to the Golgi-derived MTs is specifically stabilized compared with the centrosomal MTs 13,14 .…”

mentioning

confidence: 99%

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MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane

et al. 2014

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Recent studies have revealed the presence of a microtubule subpopulation called Golgi-derived microtubules that support Golgi ribbon formation, which is required for maintaining polarized cell migration. CLASPs and AKAP450/CG-NAP are involved in their formation, but the underlying molecular mechanisms remain unclear. Here, we find that the microtubule-crosslinking protein, MTCL1, is recruited to the Golgi membranes through interactions with CLASPs and AKAP450/CG-NAP, and promotes microtubule growth from the Golgi membrane. Correspondingly, MTCL1 knockdown specifically impairs the formation of the stable perinuclear microtubule network to which the Golgi ribbon tethers and extends. Rescue experiments demonstrate that besides its crosslinking activity mediated by the N-terminal microtubule-binding region, the C-terminal microtubule-binding region plays essential roles in these MTCL1 functions through a novel microtubule-stabilizing activity. These results suggest that MTCL1 cooperates with CLASPs and AKAP450/CG-NAP in the formation of the Golgi-derived microtubules, and mediates their development into a stable microtubule network.

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“…7). These results indicate that MTCL1 plays essential roles in the stable growing of MTs from the Golgi membrane, as has been demonstrated for CLASPs and AKAP450/ CG-NAP 8,9 .…”

supporting

confidence: 76%

mentioning

confidence: 95%

mentioning

confidence: 99%

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MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane

et al. 2014

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“…Importantly, to provide a sufficient number of microtubules for cargo exit, the TGN membranes themselves are capable of nucleating microtubules. This process is carried out by the microtubule-associated protein CLASP, which interacts with the trans-Golgi protein GCC185 (Efimov et al, 2007). To regulate microtubule nucleation, CLASP might cooperate with CLIP-170, which itself stabilizes microtubules via binding to IQGAP, and which is under the control of Cdc42 (Fukata et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Faciogenital Dysplasia Protein (FGD1) Regulates Export of Cargo Proteins from the Golgi Complex via Cdc42 Activation

Egorov

Capestrano

Vorontsova

et al. 2009

MBoC

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Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). FGD1 encodes a guanine nucleotide exchange factor that specifically activates the GTPase Cdc42. In turn, Cdc42 is an important regulator of membrane trafficking, although little is known about FGD1 involvement in this process. During development, FGD1 is highly expressed during bone growth and mineralization, and therefore a lack of the functional protein leads to a severe phenotype. Whether the secretion of proteins, which is a process essential for bone formation, is altered by mutations in FGD1 is of great interest. We initially show here that FGD1 is preferentially associated with the trans-Golgi network (TGN), suggesting its involvement in export of proteins from the Golgi. Indeed, expression of a dominant-negative FGD1 mutant and RNA interference of FGD1 both resulted in a reduction in post-Golgi transport of various cargoes (including bone-specific proteins in osteoblasts). Live-cell imaging reveals that formation of post-Golgi transport intermediates directed to the cell surface is inhibited in FGD1-deficient cells, apparently due to an impairment of TGN membrane extension along microtubules. These effects depend on FGD1 regulation of Cdc42 activation and its association with the Golgi membranes, and they may contribute to FGDY pathogenesis.

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“…Those various observations raise the possibility of a causal relationship between Golgi dysmorphology and the mitotic spindle defects that accompany hSac1 depletion. In that regard, recent work demonstrates TGN membranes have an intrinsic capability to nucleate MTs (Efimov et al, 2007). Because the TGN seems enriched in PtdIns-4-P, this raises the possibility that excess PtdIns-4-P directly results in precocious nucleation of spindle poles.…”

Section: Sac1 and Progression Through The Cell Cyclementioning

confidence: 99%

The Sac1 Phosphoinositide Phosphatase Regulates Golgi Membrane Morphology and Mitotic Spindle Organization in Mammals

Liu

Boukhelifa

Tribble

et al. 2008

MBoC

131

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Phosphoinositides (PIPs) are ubiquitous regulators of signal transduction events in eukaryotic cells. PIPs are degraded by various enzymes, including PIP phosphatases. The integral membrane Sac1 phosphatases represent a major class of such enzymes. The central role of lipid phosphatases in regulating PIP homeostasis notwithstanding, the biological functions of Sac1-phosphatases remain poorly characterized. Herein, we demonstrate that functional ablation of the single murine Sac1 results in preimplantation lethality in the mouse and that Sac1 insufficiencies result in disorganization of mammalian Golgi membranes and mitotic defects characterized by multiple mechanically active spindles. Complementation experiments demonstrate mutant mammalian Sac1 proteins individually defective in either phosphoinositide phosphatase activity, or in recycling of the enzyme from the Golgi system back to the endoplasmic reticulum, are nonfunctional proteins in vivo. The data indicate Sac1 executes an essential household function in mammals that involves organization of both Golgi membranes and mitotic spindles and that both enzymatic activity and endoplasmic reticulum localization are important Sac1 functional properties. INTRODUCTIONSpatial and temporal regulation of intracellular signaling in eukaryotic cells involves the compartmentalization of membrane surfaces into discrete, albeit often transient, functional units. There are several biochemical strategies by which cells generate such units or domains. One well-established strategy uses the chemical diversity offered by phosphoinositides (PIPs), i.e., phosphorylated forms of phosphatidylinositol (PtdIns) (Majerus, 1997;Fruman et al., 1998;Strahl and Thorner, 2007). The chemical heterogeneity of individual PIP species permits the construction of chemically unique platforms on membrane surfaces that, in turn, recruit unique cohorts of proteins that drive specific biological reactions. Spatial and temporal control of such reactions requires a finely coordinated balance between the activities of the lipid kinases that produce PIPs and the activities of enzymes that degrade them. PIP turnover is catalyzed by two general classes of enzymes: phospholipases and PIP phosphatases.Although experimental scrutiny of the phospholipases has historically been more intense, recent demonstrations of the significant biological functions played by PTEN, the myotubularins, and synaptojanins highlight the general importance of PIP phosphatases (Wishart et al., 2001;Wishart and Dixon, 2002;Wenk and De Camilli, 2004).The SAC domain derives from the yeast Sac1 protein (ySac1; Cleves et al., 1989), and it represents a signature for PIP phosphatase catalytic activity . PIP phosphatases such as phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) (Maehama et al., 2001), synaptojanins (Cremona et al., 1999), and synaptojanin-like proteins (Srinivasan et al., 1997;Stolz et al., 1998) all harbor SAC domains. The prototypical member of this family, ySac1, catalyzes the dephosphoryla...

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Asymmetric CLASP-Dependent Nucleation of Noncentrosomal Microtubules at the trans-Golgi Network

Cited by 442 publications

References 40 publications

MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane

MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane

Faciogenital Dysplasia Protein (FGD1) Regulates Export of Cargo Proteins from the Golgi Complex via Cdc42 Activation

The Sac1 Phosphoinositide Phosphatase Regulates Golgi Membrane Morphology and Mitotic Spindle Organization in Mammals

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