Null Mutants of the<i>Neurospora</i>Actin-related Protein 1 Pointed-End Complex Show Distinct Phenotypes

Lee, In Hyung; Kumar, Santosh; Plamann, Michael

doi:10.1091/mbc.12.7.2195

Cited by 55 publications

(68 citation statements)

References 44 publications

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“…The function of the p62 subunit is not fully understood, but its absence does not significantly impact dynactin stability (50). The most prominent feature of p62 is its highly conserved cysteine-rich domain (amino acids 30 -114) in the N-terminal region in which 8 of the 11 cysteines in this region form a LIM domain (49, 51, 52).…”

Section: Discussionmentioning

confidence: 99%

Copper-dependent Interaction of Dynactin Subunit p62 with the N Terminus of ATP7B but Not ATP7A

Lim

Cater

Mercer

et al. 2006

Journal of Biological Chemistry

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The P-type ATPase affected in Wilson disease, ATP7B, is a key liver protein required to regulate and maintain copper homeostasis. When hepatocytes are exposed to elevated copper levels, ATP7B traffics from the trans-Golgi network toward the biliary canalicular membrane to excrete excess copper into bile. The N-terminal region of ATP7B contains six metal-binding sites (MBS), each with the copper-binding motif MXCXXC. These sites are required for the activity and copper-regulated intracellular redistribution of ATP7B. Two proteins are known to interact with the ATP7B N-terminal region: the copper chaperone ATOX1 that delivers copper to ATP7B, and COMMD1 (MURR1) that is potentially involved in vesicular copper sequestration. To identify additional proteins that interact with ATP7B and hence are involved in copper homeostasis, a yeast twohybrid approach was employed to screen a human liver cDNA library. The dynactin subunit p62 (dynactin 4; DCTN4) was identified as an interacting partner, and this interaction was confirmed by co-immunoprecipitation from mammalian cells. The dynactin complex binds cargo, such as vesicles and organelles, to cytoplasmic dynein for retrograde microtubule-mediated trafficking and could feasibly be involved in the copper-regulated trafficking of ATP7B. The ATP7B/p62 interaction required copper, the metal-binding CXXC motifs, and the region between MBS 4 and MBS 6 of ATP7B. The p62 subunit did not interact with the related copper ATPase, ATP7A. We propose that the ATP7B interaction with p62 is a key component of the copper-induced trafficking pathway that delivers ATP7B to subapical vesicles of hepatocytes for the removal of excess copper into bile.

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Section: Discussionmentioning

confidence: 99%

Copper-dependent Interaction of Dynactin Subunit p62 with the N Terminus of ATP7B but Not ATP7A

Lim

Cater

Mercer

et al. 2006

Journal of Biological Chemistry

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“…Mutations in dynein or dynactin genes in the fungi N. crassa and Aspergillus nidulans yield the conspicuous "ropy" or "nud" (nuclear distribution) phenotypes in which nuclear transport into growing hyphae is blocked (Plamann et al, 1994;Xiang et al, 1994;Tinsley et al, 1996;Xiang et al, 1999;Lee et al, 2001). However, the microtubules in these cells are oriented with their plus ends toward the hyphal tip, the wrong orientation to support a simple dynein-based transport process.…”

Section: Discussionmentioning

confidence: 99%

“…However, the microtubules in these cells are oriented with their plus ends toward the hyphal tip, the wrong orientation to support a simple dynein-based transport process. Although N. crassa contains orthologs of p62 (Ropy-2) and p25 (Ropy-12), Ropy-12 mutants show apparently normal nuclear migration (Lee et al, 2001), leaving the function of these pointed end complex components in filamentous fungi obscure.…”

Section: Discussionmentioning

confidence: 99%

Interactions between the Evolutionarily Conserved, Actin-related Protein, Arp11, Actin, and Arp1

Eckley

Schroer

2003

MBoC

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The dynein activator dynactin is a multiprotein complex with distinct microtubule-and cargobinding domains. The cargo-binding domain contains a short, actin-like filament of the actinrelated protein Arp1, a second actin-related protein, Arp11, and conventional actin. The length of this filament is invariant in dynactin isolated from multiple species and tissues, suggesting that activities that regulate Arp1 polymerization are important for dynactin assembly. Arp11 is present in a protein complex localized at the pointed end of the Arp1 minifilament, whereas actin capping protein (CapZ) is present at the barbed end. Either might cooperate with conventional actin to cap Arp1. We tested the ability of Arp11 to interact with conventional actin and found it could coassemble. Like Arp1, cytosolic Arp11 is found only in dynactin, suggesting that Arp11 and free cytosolic actin do not interact significantly. Recombinant Arp11 and Arp1 were demonstrated to interact by coprecipitation. We developed an in vivo assay for Arp11-Arp1 interaction based on previous observations that Arp1 forms filamentous assemblies when overexpressed in cultured cells. Arp11 significantly decreases the formation of these organized Arp1 assemblies. Finally, this assay was used to confirm the identity of a putative Arp11 homolog in Drosophila melanogaster.

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“…If they exist in budding yeast, they may be found by physical association with Arp10p or by genetic interactions. Budding yeast and Neurospora crassa dynactin have similar sedimentation coefficients (15.5S and 15S, respectively) (Kahana et al, 1998;Lee et al, 2001), and N. crassa dynactin is known to include all key subunits of dynactin, including a pointed-end complex. Thus, the smaller size of the yeast dynactin complex (relative to the 20S vertebrate complex) (Karki and Holzbaur, 1999) does not rule out the existence of a pointed-end complex.…”

Section: A Possible Pointed-end Complex In Budding Yeastmentioning

confidence: 99%

Arp10p Is a Pointed-End-associated Component of Yeast Dynactin

Clark

Rose

2006

MBoC

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In metazoans, dynein-dependent vesicle transport is mediated by dynactin, containing an actin-related protein, Arp1p, together with a cargo-selection complex containing a second actin-related protein, Arp11. Paradoxically, in budding yeast, models of dynactin function imply an interaction with membranes, whereas the lack of microtubule-based vesicle transport implies the absence of a cargo-selection complex. Using both genetic and biochemical approaches, we demonstrate that Arp10p is the functional yeast homologue of Arp11, suggesting the possible existence of a pointed-end complex in yeast. Specifically, Arp10p interacts with Arp1p and other dynactin subunits and is dependent on Arp1p for stability. Conversely, Arp10p stabilizes the dynactin complex by association with the Arp1p filament pointed end. Using a novel hRAS-Arp1p one-hybrid assay, we show that Arp1p associates with the plasma membrane dependent on dynactin subunits, but independent of dynein, and sensitive to cell wall damage. We directly show the association of Arp1p with not only the plasma membrane but also with a less dense membrane fraction. Based on the hRAS-Arp1p assay, loss of Arp10p enhances the apparent association of dynactin with the plasma membrane and suppresses the loss of signaling conferred by cell wall damage.

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Null Mutants of theNeurosporaActin-related Protein 1 Pointed-End Complex Show Distinct Phenotypes

Cited by 55 publications

References 44 publications

Copper-dependent Interaction of Dynactin Subunit p62 with the N Terminus of ATP7B but Not ATP7A

Copper-dependent Interaction of Dynactin Subunit p62 with the N Terminus of ATP7B but Not ATP7A

Interactions between the Evolutionarily Conserved, Actin-related Protein, Arp11, Actin, and Arp1

Arp10p Is a Pointed-End-associated Component of Yeast Dynactin

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