Abstract
Axonal transport of membranous organelles such as mitochondria is essential for neuron viability and function. How signaling mechanisms regulate or influence mitochondrial distribution and transport is still largely unknown. We observed an increase in the distal distribution of mitochondria in neurons upon the expression of pleckstrin homology (PH) domains of phospholipase Cδ1 (PLCδ-PH) and spectrin (spectrin-PH). Quantitative analysis of mitochondrial transport showed that specific binding of PH domains to phosphatidylinositol (4,5) bisphosphate (PtdIns(4,5)P2) but not 3′ phosphorylated phosphatidylinositol species enhanced plus-end - directed transport of mitochondria two- to threefold and at the same time decreased minus-end - directed transport of mitochondria along axonal microtubules (MTs) without altering the overall level of motility. Further, the velocity and duration of mitochondrial transport plus the association of molecular motors with mitochondria remained unchanged by the expression of PH domains. Thus, PtdIns(4,5)P2-specific PH domains caused an increase in distal mitochondria by disturbing the balance of plus- and minus-end - directed transport rather than directly affecting the molecular machinery involved. Taken together our data reveal that level and directionality of transport are separable and that PtdIns(4,5)P2 has a novel role in regulation of the directionality of axonal transport of mitochondria.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3636-3649 |
| Number of pages | 14 |
| Journal | Molecular Biology of the Cell |
| Volume | 14 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cell Biology
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Expression of phosphatidylinositol (4,5) bisphosphate-specific pleckstrin homology domains alters direction but not the level of axonal transport of mitochondria. / De Vos, Kurt J.; Sable, Julia; Miller, Kyle E.; Sheetz, Michael.
In: Molecular Biology of the Cell, Vol. 14, No. 9, 01.09.2003, p. 3636-3649.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of phosphatidylinositol (4,5) bisphosphate-specific pleckstrin homology domains alters direction but not the level of axonal transport of mitochondria
AU - De Vos, Kurt J.
AU - Sable, Julia
AU - Miller, Kyle E.
AU - Sheetz, Michael
PY - 2003/9/1
Y1 - 2003/9/1
N2 - Axonal transport of membranous organelles such as mitochondria is essential for neuron viability and function. How signaling mechanisms regulate or influence mitochondrial distribution and transport is still largely unknown. We observed an increase in the distal distribution of mitochondria in neurons upon the expression of pleckstrin homology (PH) domains of phospholipase Cδ1 (PLCδ-PH) and spectrin (spectrin-PH). Quantitative analysis of mitochondrial transport showed that specific binding of PH domains to phosphatidylinositol (4,5) bisphosphate (PtdIns(4,5)P2) but not 3′ phosphorylated phosphatidylinositol species enhanced plus-end - directed transport of mitochondria two- to threefold and at the same time decreased minus-end - directed transport of mitochondria along axonal microtubules (MTs) without altering the overall level of motility. Further, the velocity and duration of mitochondrial transport plus the association of molecular motors with mitochondria remained unchanged by the expression of PH domains. Thus, PtdIns(4,5)P2-specific PH domains caused an increase in distal mitochondria by disturbing the balance of plus- and minus-end - directed transport rather than directly affecting the molecular machinery involved. Taken together our data reveal that level and directionality of transport are separable and that PtdIns(4,5)P2 has a novel role in regulation of the directionality of axonal transport of mitochondria.
AB - Axonal transport of membranous organelles such as mitochondria is essential for neuron viability and function. How signaling mechanisms regulate or influence mitochondrial distribution and transport is still largely unknown. We observed an increase in the distal distribution of mitochondria in neurons upon the expression of pleckstrin homology (PH) domains of phospholipase Cδ1 (PLCδ-PH) and spectrin (spectrin-PH). Quantitative analysis of mitochondrial transport showed that specific binding of PH domains to phosphatidylinositol (4,5) bisphosphate (PtdIns(4,5)P2) but not 3′ phosphorylated phosphatidylinositol species enhanced plus-end - directed transport of mitochondria two- to threefold and at the same time decreased minus-end - directed transport of mitochondria along axonal microtubules (MTs) without altering the overall level of motility. Further, the velocity and duration of mitochondrial transport plus the association of molecular motors with mitochondria remained unchanged by the expression of PH domains. Thus, PtdIns(4,5)P2-specific PH domains caused an increase in distal mitochondria by disturbing the balance of plus- and minus-end - directed transport rather than directly affecting the molecular machinery involved. Taken together our data reveal that level and directionality of transport are separable and that PtdIns(4,5)P2 has a novel role in regulation of the directionality of axonal transport of mitochondria.
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UR - http://www.scopus.com/inward/citedby.url?scp=0141521642&partnerID=8YFLogxK
U2 - 10.1091/mbc.E02-10-0638
DO - 10.1091/mbc.E02-10-0638
M3 - Article
C2 - 12972553
AN - SCOPUS:0141521642
VL - 14
SP - 3636
EP - 3649
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 9
ER -