TY - JOUR
T1 - A conserved mechanism for mitochondria-dependent dynein anchoring
AU - Kraft, Lauren M.
AU - Lackner, Laura L.
N1 - Funding Information:
We thank Yoko Shibata and Rick Morimoto for S. pombe strains and advice, Rishi Jajoo for sharing plasmid pRJ06, Snezhana Oliferenko for sharing plasmid mCherry-AHDL, and Jessica Hornick and instrumentation support from the Biological Imaging Facility at Northwestern University. L.M.K. is supported by National Institutes of Health National Institute of General Medical Sciences (NIH NIGMS) Training Grant no. T32GM-008061. L.L.L. is supported by NIH NIGMS Grant no. R01GM-120303 and the Robert H. Lurie Comprehensive Cancer Center-The Lefkofsky Family Foundation/Liz and Eric Lefkofsky Innovation Research Award
Funding Information:
We thank members of the Lackner lab, Jennifer Brace, members of the Weiss lab, and the WiLa ICB for suggestions and critical scientific discussions. We thank Heidi Schmit-Anderson for help with graphing in R. We thank Yoko Shibata and Rick Morimoto for S. pombe strains and advice, Rishi Jajoo for sharing plasmid pRJ06, Snezhana Oliferenko for sharing plasmid mCherry-AHDL, and Jessica Hornick and instrumentation support from the Biological Imaging Facility at Northwestern University. L.M.K. is supported by National Institutes of Health National Institute of General Medical Sciences (NIH NIGMS) Training Grant no. T32GM-008061. L.L.L. is supported by NIH NIGMS Grant no. R01GM-120303 and the Robert H. Lurie Comprehensive Cancer Center–The Lefkofsky Family Foundation/Liz and Eric Lefkofsky Innovation Research Award.
Publisher Copyright:
© 2019 Kraft and Lackner.
PY - 2019
Y1 - 2019
N2 - Mitochondrial anchors have functions that extend beyond simply positioning mitochondria. In budding yeast, mitochondria drive the assembly of the mitochondrial anchor protein Num1 into clusters, which serve to anchor mitochondria as well as dynein to the cell cortex. Here, we explore a conserved role for mitochondria in dynein anchoring by examining the tethering functions of the evolutionarily distant Schizosaccharomyces pombe Num1 homologue. In addition to its function in dynein anchoring, we find that S. pombe Num1, also known as Mcp5, interacts with and tethers mitochondria to the plasma membrane in S. pombe and Saccharomyces cerevisiae. Thus, the mitochondria and plasma membrane-binding domains of the Num1 homologues, as well as the membrane features these domains recognize, are conserved. In S. pombe, we find that mitochondria impact the assembly and cellular distribution of Num1 clusters and that Num1 clusters actively engaged in mitochondrial tethering serve as cortical attachment sites for dynein. Thus, mitochondria play a critical and conserved role in the formation and distribution of dynein-anchoring sites at the cell cortex and, as a consequence, impact dynein function. These findings shed light on an ancient mechanism of mitochondria-dependent dynein anchoring that is conserved over more than 450 million years of evolution, raising the intriguing possibility that the role mitochondria play in dynein anchoring and function extends beyond yeast to higher eukaryotes.
AB - Mitochondrial anchors have functions that extend beyond simply positioning mitochondria. In budding yeast, mitochondria drive the assembly of the mitochondrial anchor protein Num1 into clusters, which serve to anchor mitochondria as well as dynein to the cell cortex. Here, we explore a conserved role for mitochondria in dynein anchoring by examining the tethering functions of the evolutionarily distant Schizosaccharomyces pombe Num1 homologue. In addition to its function in dynein anchoring, we find that S. pombe Num1, also known as Mcp5, interacts with and tethers mitochondria to the plasma membrane in S. pombe and Saccharomyces cerevisiae. Thus, the mitochondria and plasma membrane-binding domains of the Num1 homologues, as well as the membrane features these domains recognize, are conserved. In S. pombe, we find that mitochondria impact the assembly and cellular distribution of Num1 clusters and that Num1 clusters actively engaged in mitochondrial tethering serve as cortical attachment sites for dynein. Thus, mitochondria play a critical and conserved role in the formation and distribution of dynein-anchoring sites at the cell cortex and, as a consequence, impact dynein function. These findings shed light on an ancient mechanism of mitochondria-dependent dynein anchoring that is conserved over more than 450 million years of evolution, raising the intriguing possibility that the role mitochondria play in dynein anchoring and function extends beyond yeast to higher eukaryotes.
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U2 - 10.1091/mbc.E18-07-0466
DO - 10.1091/mbc.E18-07-0466
M3 - Article
C2 - 30649994
AN - SCOPUS:85063369867
VL - 30
SP - 691
EP - 702
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 5
ER -