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Organelle segregation during mitosis: lessons from asymmetrically dividing cells.

Ouellet J, Barral Y - J. Cell Biol. (2012)

Bottom Line: Analysis of organelle partitioning in asymmetrically dividing cells has provided insights into the mechanisms through which cells control organelle distribution.Interestingly, these studies have revealed that segregation mechanisms frequently link organelle distribution to organelle growth and formation.Furthermore, in many cases, cells use organelles, such as the endoplasmic reticulum and P granules, as vectors for the segregation of information.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, 8093 Zurich, Switzerland.

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Two models for the formation of aggresomes. (A, top) In the transport model, small cytoplasmic aggregates are formed throughout the cell and accumulate the chaperone protein Hsp104. The association with Hsp104 is required for the loading of the small aggregates onto microtubules and their transport to the centrosome in a dynein-dependent manner. At this location, the small aggregates merge with the aggresome. In this model, Hsp104 is active everywhere. (B, top) In the dissociation/condensation model, Hsp104 activity is high throughout the cytoplasm and on the small aggregates formed, whereas it is low on the aggresome. Therefore, the small aggregates rapidly release their material for incorporation in the aggresome. In this model, microtubules may mediate the transport of an Hsp104 inhibitor to the centrosome to allow aggresome condensation at this place. (A and B, bottom illustrations) Predictions for the effects of Hsp104 inhibiting in each model. Inhibition of Hsp104 leads to formation of smaller aggregates throughout the cytoplasm. In the transport model (A, bottom), this is because of the fact that they are no longer transported to the centrosome. In the dissociation model (B, bottom), condensation occurs throughout the cytoplasm.
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fig2: Two models for the formation of aggresomes. (A, top) In the transport model, small cytoplasmic aggregates are formed throughout the cell and accumulate the chaperone protein Hsp104. The association with Hsp104 is required for the loading of the small aggregates onto microtubules and their transport to the centrosome in a dynein-dependent manner. At this location, the small aggregates merge with the aggresome. In this model, Hsp104 is active everywhere. (B, top) In the dissociation/condensation model, Hsp104 activity is high throughout the cytoplasm and on the small aggregates formed, whereas it is low on the aggresome. Therefore, the small aggregates rapidly release their material for incorporation in the aggresome. In this model, microtubules may mediate the transport of an Hsp104 inhibitor to the centrosome to allow aggresome condensation at this place. (A and B, bottom illustrations) Predictions for the effects of Hsp104 inhibiting in each model. Inhibition of Hsp104 leads to formation of smaller aggregates throughout the cytoplasm. In the transport model (A, bottom), this is because of the fact that they are no longer transported to the centrosome. In the dissociation model (B, bottom), condensation occurs throughout the cytoplasm.

Mentions: Aggresomes are a second type of organelle that segregate asymmetrically at mitosis (Macara and Mili, 2008). The aggresome is formed of ubiquitinated and aggregating misfolded proteins and is characterized by the accumulation of the proteasome on its surface (Fig. 2; Johnston et al., 1998; Wigley et al., 1999; Garcia-Mata et al., 2002). Whereas the aggresome is constitutively present in some cell types such as HEK293 and HeLa cells (Wigley et al., 1999), in other cells, its formation is induced by the expression of proteins that fold inefficiently (such as mutant or poly-Q/N–rich proteins) or through inhibition of the ubiquitin-dependent degradation pathway (Bence et al., 2001; Chiti and Dobson, 2006; Gidalevitz et al., 2006; Link et al., 2006). Therefore, the aggresome is thought to accumulate misfolded and aggregating proteins that the cell is not able to properly degrade, particularly amyloid structures. It generally localizes as a single entity to the vicinity of the centrosome and therefore segregates with only one of the two spindle poles at mitosis (Wigley et al., 1999). Its asymmetric segregation is thought to help clear one of the two daughter cells, generally the self-renewing stem cell, from damaged and potentially damaging proteins. Current models suggest that aggresome formation results from the transport of smaller aggregates to the centrosome and their accumulation around it (Fig. 2 A, top). In favor of such a scenario, cells lacking microtubules or the microtubule-dependent motor protein dynein fail to assemble an aggresome but instead display smaller aggregates throughout the cell (Johnston et al., 1998, 2002; García-Mata et al., 1999). This phenotype is very reminiscent of that of cells lacking chaperones, such as Hsp104 in yeast. Thus, beyond their function in disaggregating these chaperones, Hsp104 might also function in the transport of the aggregating proteins, perhaps by acting as an adaptor between them and transport motors such as dynein (Fig. 2 A, bottom). However, it is unclear whether microtubules and motor activity are required for transport and delivery of aggresome constituents or rather for the localization of a condensation activity required for aggresome assembly.


Organelle segregation during mitosis: lessons from asymmetrically dividing cells.

Ouellet J, Barral Y - J. Cell Biol. (2012)

Two models for the formation of aggresomes. (A, top) In the transport model, small cytoplasmic aggregates are formed throughout the cell and accumulate the chaperone protein Hsp104. The association with Hsp104 is required for the loading of the small aggregates onto microtubules and their transport to the centrosome in a dynein-dependent manner. At this location, the small aggregates merge with the aggresome. In this model, Hsp104 is active everywhere. (B, top) In the dissociation/condensation model, Hsp104 activity is high throughout the cytoplasm and on the small aggregates formed, whereas it is low on the aggresome. Therefore, the small aggregates rapidly release their material for incorporation in the aggresome. In this model, microtubules may mediate the transport of an Hsp104 inhibitor to the centrosome to allow aggresome condensation at this place. (A and B, bottom illustrations) Predictions for the effects of Hsp104 inhibiting in each model. Inhibition of Hsp104 leads to formation of smaller aggregates throughout the cytoplasm. In the transport model (A, bottom), this is because of the fact that they are no longer transported to the centrosome. In the dissociation model (B, bottom), condensation occurs throughout the cytoplasm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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Show All Figures
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fig2: Two models for the formation of aggresomes. (A, top) In the transport model, small cytoplasmic aggregates are formed throughout the cell and accumulate the chaperone protein Hsp104. The association with Hsp104 is required for the loading of the small aggregates onto microtubules and their transport to the centrosome in a dynein-dependent manner. At this location, the small aggregates merge with the aggresome. In this model, Hsp104 is active everywhere. (B, top) In the dissociation/condensation model, Hsp104 activity is high throughout the cytoplasm and on the small aggregates formed, whereas it is low on the aggresome. Therefore, the small aggregates rapidly release their material for incorporation in the aggresome. In this model, microtubules may mediate the transport of an Hsp104 inhibitor to the centrosome to allow aggresome condensation at this place. (A and B, bottom illustrations) Predictions for the effects of Hsp104 inhibiting in each model. Inhibition of Hsp104 leads to formation of smaller aggregates throughout the cytoplasm. In the transport model (A, bottom), this is because of the fact that they are no longer transported to the centrosome. In the dissociation model (B, bottom), condensation occurs throughout the cytoplasm.
Mentions: Aggresomes are a second type of organelle that segregate asymmetrically at mitosis (Macara and Mili, 2008). The aggresome is formed of ubiquitinated and aggregating misfolded proteins and is characterized by the accumulation of the proteasome on its surface (Fig. 2; Johnston et al., 1998; Wigley et al., 1999; Garcia-Mata et al., 2002). Whereas the aggresome is constitutively present in some cell types such as HEK293 and HeLa cells (Wigley et al., 1999), in other cells, its formation is induced by the expression of proteins that fold inefficiently (such as mutant or poly-Q/N–rich proteins) or through inhibition of the ubiquitin-dependent degradation pathway (Bence et al., 2001; Chiti and Dobson, 2006; Gidalevitz et al., 2006; Link et al., 2006). Therefore, the aggresome is thought to accumulate misfolded and aggregating proteins that the cell is not able to properly degrade, particularly amyloid structures. It generally localizes as a single entity to the vicinity of the centrosome and therefore segregates with only one of the two spindle poles at mitosis (Wigley et al., 1999). Its asymmetric segregation is thought to help clear one of the two daughter cells, generally the self-renewing stem cell, from damaged and potentially damaging proteins. Current models suggest that aggresome formation results from the transport of smaller aggregates to the centrosome and their accumulation around it (Fig. 2 A, top). In favor of such a scenario, cells lacking microtubules or the microtubule-dependent motor protein dynein fail to assemble an aggresome but instead display smaller aggregates throughout the cell (Johnston et al., 1998, 2002; García-Mata et al., 1999). This phenotype is very reminiscent of that of cells lacking chaperones, such as Hsp104 in yeast. Thus, beyond their function in disaggregating these chaperones, Hsp104 might also function in the transport of the aggregating proteins, perhaps by acting as an adaptor between them and transport motors such as dynein (Fig. 2 A, bottom). However, it is unclear whether microtubules and motor activity are required for transport and delivery of aggresome constituents or rather for the localization of a condensation activity required for aggresome assembly.

Bottom Line: Analysis of organelle partitioning in asymmetrically dividing cells has provided insights into the mechanisms through which cells control organelle distribution.Interestingly, these studies have revealed that segregation mechanisms frequently link organelle distribution to organelle growth and formation.Furthermore, in many cases, cells use organelles, such as the endoplasmic reticulum and P granules, as vectors for the segregation of information.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, 8093 Zurich, Switzerland.

Show MeSH
Related in: MedlinePlus