Control of Organelle Size: The Golgi Complex
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15232, USA. Annual Review of Cell and Developmental Biology
(Impact Factor: 16.66).
05/2011; 27(1):57-77. DOI: 10.1146/annurev-cellbio-100109-104003
The Golgi complex processes secretory proteins and lipids, carries out protein sorting and signaling, and supports growth and composition of the plasma membrane. Golgi complex size likely is regulated to meet the demands of each function, and this may involve differential changes of its distinct subdomains. Nevertheless, the primary size change is elongation of the Golgi ribbon-like network as occurs during Golgi complex doubling for mitosis and during differentiation involving upregulated secretion. One hypothesis states that Golgi complex size is set by the abundance of secretory cargo and Golgi complex components that, through binding vesicle coat complexes, drive vesicle coat formation to alter Golgi complex influx and efflux. Regulation of transport factors controlling Golgi membrane traffic is also observed and may control Golgi complex size, but more work is needed to directly link these events to Golgi complex size regulation, especially during differentiation of specialized cell types.
Available from: Vedrana Tadic
- "The function of the Golgi complex has been shown to be strongly intertwined with the morphology and size of the organelle (Sengupta and Linstedt, 2011). Fragmentation of the Golgi complex has been implemented in neurodegenerative diseases, like "
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ABSTRACT: The function of intact organelles, whether mitochondria, Golgi apparatus or endoplasmic reticulum (ER), relies on their proper morphological organization. It is recognized that disturbances of organelle morphology are early events in disease manifestation, but reliable and quantitative detection of organelle morphology is difficult and time-consuming. Herewe present a novel computer vision algorithm for the assessment of organelle morphology inwhole cell 3D images. The algorithm allows the numerical and quantitative description of organelle structures, including total number and length of segments, cell and nucleus area/volume as well as novel texture parameters like lacunarity and fractal dimension. Applying the algorithm we performed a pilot study in cultured motor neurons from transgenic G93A hSOD1 mice, a model of human familial amyotrophic lateral sclerosis. In the presence of the mutated SOD1 and upon excitotoxic treatment with kainate we demonstrate a clear fragmentation of the mitochondrial network, with an increase in the number of mitochondrial segments and a reduction in the length of mitochondria. Histogram analyses show a reduced number of tubular mitochondria and an increased number of small mitochondrial segments. The computer vision algorithmfor the evaluation of organellemorphology allows an objective assessment of disease-related organelle phenotypes with greatly reduced examiner bias and will aid the evaluation of novel therapeutic strategies on a cellular level.
Available from: Elize Haasdijk
- "The Golgi apparatus is a highly dynamic organelle involved in processing and sorting of lipids and proteins. Its morphology depends on a large variety of protein components and cellular processes [9-13]. Accordingly, Golgi morphology can alter under a variety of physiological conditions such as cell division, growth, and altered metabolic demands , as well as pathological conditions, including impaired ER function, disruption of intracellular transport, altered lipid metabolism, excessive excitation, DNA damage, and activation of cell death pathways [6,14-19]. "
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ABSTRACT: Fragmentation of stacked cisterns of the Golgi apparatus into dispersed smaller elements is a feature associated with degeneration of neurons in amyotrophic lateral sclerosis (ALS) and some other neurodegenerative disorders. However, the role of Golgi fragmentation in motor neuron degeneration is not well understood.
Here we use a SOD1-ALS mouse model (low-copy Gurney G93A-SOD1 mouse) to show that motor neurons with Golgi fragmentation are retrogradely labeled by intramuscularly injected CTB (beta subunit of cholera toxin), indicating that Golgi fragmentation precedes neuromuscular denervation and axon retraction. We further show that Golgi fragmentation may occur in the absence of and precede two other pathological markers, i.e. somatodendritic SOD1 inclusions, and the induction of ATF3 expression. In addition, we show that Golgi fragmentation is associated with an altered dendritic organization of the Golgi apparatus, does not depend on intact apoptotic machinery, and is facilitated in transgenic mice with impaired retrograde dynein-dependent transport (BICD2-N mice). A connection to altered dynein-dependent transport also is suggested by reduced expression of endosomal markers in neurons with Golgi fragmentation, which also occurs in neurons with impaired dynein function.
Together the data indicate that Golgi fragmentation is a very early event in the pathological cascade in ALS that is associated with altered organization of intracellular trafficking.
Available from: Catherine I Dumur
- "Ultrastructural analysis performed in Rab1b-transfected cells (Figure 1) indicates that the Golgi ribbon goes through an elongation process, while the number of cisternae per stack and the cisternal surface area seem to remain unchanged. Golgi ribbon elongation occurs during cell growth and differentiation and takes place through growth of additional ministacks after an increased synthesis of Golgi complex proteins (Sengupta and Linstedt, 2011). In agreement, Rab1b overexpression increases GM130/GOLGA2 mRNA and protein levels (Table 2 and Figure 3, respectively). "
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ABSTRACT: Rab1b belongs to the Rab-GTPase family that regulates membrane trafficking and signal transduction systems able to control diverse cellular activities including gene expression. Rab1b is essential for ER-Golgi transport. Although it is ubiquitously expressed, its mRNA levels vary among different tissues. This work aims to characterize the role of the high Rab1b levels detected in some secretory tissues. We report that, in HeLa cells, an increase in Rab1b levels induces changes in Golgi size and gene expression. Significantly, analyses applied to selected genes, KDELR3, GM130 (involved in membrane transport) and the proto-oncogene JUN, indicate that the Rab1b increase acts as a molecular switch to control their expression at the transcriptional level, resulting in changes at the protein level. These Rab1b-dependent changes require the activity of p38 MAPK and the CREB consensus binding site in those target promoter regions. Moreover, our results reveal that, in a secretory thyroid cell line (FRTL5), Rab1b expression increases in response to thyroid-stimulating hormone (TSH). Additionally, changes in Rab1b expression in FRTL5 cells modify the specific TSH-response. Our results show, for the first time, that changes in Rab1b levels modulate gene transcription and strongly suggest that a Rab1b increase is required to elicit a secretory response.
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