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Dynein-dynactin complex is essential for dendritic restriction of TM1-containing Drosophila Dscam.

Yang JS, Bai JM, Lee T - PLoS ONE (2008)

Bottom Line: In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl.Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites.The results of this study suggest multiple mechanisms of dendritic protein targeting.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA, USA.

ABSTRACT

Background: Many membrane proteins, including Drosophila Dscam, are enriched in dendrites or axons within neurons. However, little is known about how the differential distribution is established and maintained.

Methodology/principal findings: Here we investigated the mechanisms underlying the dendritic targeting of Dscam[TM1]. Through forward genetic mosaic screens and by silencing specific genes via targeted RNAi, we found that several genes, encoding various components of the dynein-dynactin complex, are required for restricting Dscam[TM1] to the mushroom body dendrites. In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl. Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites.

Conclusions/significance: The results of this study suggest multiple mechanisms of dendritic protein targeting. Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport.

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Related in: MedlinePlus

Mistargeting of dendritic Dscam in Group I mutant clones.MB clones of different complementation groups of group I. Granular accumulation of Dscam[TM1]::GFP (green) in the MB lobes was observed in four of the six complementation groups, including Lis1, Dmn, p24 and DB-D10 (A–C and G, arrows). In contrast, mistargeted Dscam preferentially accumulated in the peduncles of DC-B9 mutant clones (H, arrow), while Dscam[TM1]::GFP was rather uniformly distributed in AC-E10 clones (I, arrows). MB clones were co-labeled by mCD8::RFP (red). Note the reduced dendritic region in Lis1 mutant clone (arrowhead).
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pone-0003504-g002: Mistargeting of dendritic Dscam in Group I mutant clones.MB clones of different complementation groups of group I. Granular accumulation of Dscam[TM1]::GFP (green) in the MB lobes was observed in four of the six complementation groups, including Lis1, Dmn, p24 and DB-D10 (A–C and G, arrows). In contrast, mistargeted Dscam preferentially accumulated in the peduncles of DC-B9 mutant clones (H, arrow), while Dscam[TM1]::GFP was rather uniformly distributed in AC-E10 clones (I, arrows). MB clones were co-labeled by mCD8::RFP (red). Note the reduced dendritic region in Lis1 mutant clone (arrowhead).

Mentions: Detailed analysis of group 1 mutants further revealed subclasses of misdistribution phenotypes. Five of the nine mutants exhibited granular accumulation of Dscam[TM1]::GFP in the MB lobes (e.g. Figures 2A–2C and 2G), three had Dscam[TM1]::GFP selectively accumulated in the peduncle (e.g. Figure 2H), and the last one showed broad non-granular distribution of Dscam[TM1]::GFP (e.g. Figure 2I). In addition, many of the mutant clones were smaller than controls (e.g. Figure 1H). Two of the lines with granular accumulation had reduced calycal volume, suggesting possible defects in dendritic morphogenesis. These phenomena indicate that genes involved in dendritic protein targeting potentially underlie multiple fundamental cellular functions. Further, the identification of several clusters of misdistribution phenotypes suggests the involvement of multiple mechanisms in restricting Dscam[TM1] to dendrites. However, distinct phenotypes might simply result from allele variations in genes of similar function.


Dynein-dynactin complex is essential for dendritic restriction of TM1-containing Drosophila Dscam.

Yang JS, Bai JM, Lee T - PLoS ONE (2008)

Mistargeting of dendritic Dscam in Group I mutant clones.MB clones of different complementation groups of group I. Granular accumulation of Dscam[TM1]::GFP (green) in the MB lobes was observed in four of the six complementation groups, including Lis1, Dmn, p24 and DB-D10 (A–C and G, arrows). In contrast, mistargeted Dscam preferentially accumulated in the peduncles of DC-B9 mutant clones (H, arrow), while Dscam[TM1]::GFP was rather uniformly distributed in AC-E10 clones (I, arrows). MB clones were co-labeled by mCD8::RFP (red). Note the reduced dendritic region in Lis1 mutant clone (arrowhead).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2566808&req=5

pone-0003504-g002: Mistargeting of dendritic Dscam in Group I mutant clones.MB clones of different complementation groups of group I. Granular accumulation of Dscam[TM1]::GFP (green) in the MB lobes was observed in four of the six complementation groups, including Lis1, Dmn, p24 and DB-D10 (A–C and G, arrows). In contrast, mistargeted Dscam preferentially accumulated in the peduncles of DC-B9 mutant clones (H, arrow), while Dscam[TM1]::GFP was rather uniformly distributed in AC-E10 clones (I, arrows). MB clones were co-labeled by mCD8::RFP (red). Note the reduced dendritic region in Lis1 mutant clone (arrowhead).
Mentions: Detailed analysis of group 1 mutants further revealed subclasses of misdistribution phenotypes. Five of the nine mutants exhibited granular accumulation of Dscam[TM1]::GFP in the MB lobes (e.g. Figures 2A–2C and 2G), three had Dscam[TM1]::GFP selectively accumulated in the peduncle (e.g. Figure 2H), and the last one showed broad non-granular distribution of Dscam[TM1]::GFP (e.g. Figure 2I). In addition, many of the mutant clones were smaller than controls (e.g. Figure 1H). Two of the lines with granular accumulation had reduced calycal volume, suggesting possible defects in dendritic morphogenesis. These phenomena indicate that genes involved in dendritic protein targeting potentially underlie multiple fundamental cellular functions. Further, the identification of several clusters of misdistribution phenotypes suggests the involvement of multiple mechanisms in restricting Dscam[TM1] to dendrites. However, distinct phenotypes might simply result from allele variations in genes of similar function.

Bottom Line: In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl.Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites.The results of this study suggest multiple mechanisms of dendritic protein targeting.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA, USA.

ABSTRACT

Background: Many membrane proteins, including Drosophila Dscam, are enriched in dendrites or axons within neurons. However, little is known about how the differential distribution is established and maintained.

Methodology/principal findings: Here we investigated the mechanisms underlying the dendritic targeting of Dscam[TM1]. Through forward genetic mosaic screens and by silencing specific genes via targeted RNAi, we found that several genes, encoding various components of the dynein-dynactin complex, are required for restricting Dscam[TM1] to the mushroom body dendrites. In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl. Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites.

Conclusions/significance: The results of this study suggest multiple mechanisms of dendritic protein targeting. Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport.

Show MeSH
Related in: MedlinePlus