Limits...
A new role of multi scaffold protein Liprin-α: Liprin-α suppresses Rho-mDia mediated stress fiber formation.

Sakamoto S, Narumiya S, Ishizaki T - Bioarchitecture (2012)

Bottom Line: Mammalian homolog of Diaphanous (mDia) is one of the Rho effectors and produces unbranched actin filaments.In our recent paper, we identified Liprin-α as an mDia interacting protein and found that Liprin-α negatively regulates the activity of mDia in the cell by displacing it from the plasma membrane through binding to the DID-DD region of mDia.Here, we review these findings and discuss how Liprin-α regulates the Rho-mDia pathway and how the mDia-Liprin-α complex functions in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology; Kyoto University Graduate School of Medicine; Kyoto, Japan.

ABSTRACT
Regulation of the actin cytoskeleton is crucial for cell morphology and migration. One of the key molecules that regulates actin remodeling is the small GTPase Rho. Rho shuttles between the inactive GDP-bound form and the active GTP-bound form, and works as a molecular switch in actin remodeling in response to both extra- and intra-cellular stimuli. Mammalian homolog of Diaphanous (mDia) is one of the Rho effectors and produces unbranched actin filaments. While Rho GTPases activate mDia, the mechanisms of how the activity of mDia is downregulated in cells remains largely unknown. In our recent paper, we identified Liprin-α as an mDia interacting protein and found that Liprin-α negatively regulates the activity of mDia in the cell by displacing it from the plasma membrane through binding to the DID-DD region of mDia. Here, we review these findings and discuss how Liprin-α regulates the Rho-mDia pathway and how the mDia-Liprin-α complex functions in vivo.

No MeSH data available.


Figure 4. Liprin phylogenetic tree. Phylogram was generated by Genetyx of the evolutionary distances between the three Drosophila Liprins and their closest human and mouse homologs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3383721&req=5

Figure 4: Figure 4. Liprin phylogenetic tree. Phylogram was generated by Genetyx of the evolutionary distances between the three Drosophila Liprins and their closest human and mouse homologs.

Mentions: Liprin was first identified as an interacting protein of the leukocyte common antigen-related (LAR) family of receptor protein tyrosine phosphatase in 1995.24 Liprin is composed of the coiled-coil domain in the N-terminus and three consecutive sterile-α-motif (SAM) domains (often referred to as Liprin homology domain) in the C-terminus (Fig. 3). The second SAM domain of liprin-α interacts with the intracellular domain of LAR. Liprin is a large family of proteins that are classified into three types: Liprin-α, Liprin-β and KazrinE (Fig. 4). Vertebrate contain four Liprin-αs (α1–4), two Liprin-βs (β1, 2) and KazrinE. Drosophila and Xenopus also have three types of Liprins: Liprin-α, β, and γ. KazrinE and Liprin-γ have been recently identified as a third type of protein related to the Liprin family.25-28 Among four isoforms of Kazrin (KazrinA, B, C and E) only KazrinE contains the Liprin-α homology domain.27 In mammals, Liprin-α1, Liprin-β1 and β2 are expressed ubiquitously, whereas, Liprin-α2 and α3 are mainly expressed in the brain, and Liprin-α4 is in the brain, heart and skeletal muscle.25 In contrast, C. elegans contains only one Liprin-α, called syd-2 (synapse defective-2), which shares 50% identity to human Liprin-α1.


A new role of multi scaffold protein Liprin-α: Liprin-α suppresses Rho-mDia mediated stress fiber formation.

Sakamoto S, Narumiya S, Ishizaki T - Bioarchitecture (2012)

Figure 4. Liprin phylogenetic tree. Phylogram was generated by Genetyx of the evolutionary distances between the three Drosophila Liprins and their closest human and mouse homologs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3383721&req=5

Figure 4: Figure 4. Liprin phylogenetic tree. Phylogram was generated by Genetyx of the evolutionary distances between the three Drosophila Liprins and their closest human and mouse homologs.
Mentions: Liprin was first identified as an interacting protein of the leukocyte common antigen-related (LAR) family of receptor protein tyrosine phosphatase in 1995.24 Liprin is composed of the coiled-coil domain in the N-terminus and three consecutive sterile-α-motif (SAM) domains (often referred to as Liprin homology domain) in the C-terminus (Fig. 3). The second SAM domain of liprin-α interacts with the intracellular domain of LAR. Liprin is a large family of proteins that are classified into three types: Liprin-α, Liprin-β and KazrinE (Fig. 4). Vertebrate contain four Liprin-αs (α1–4), two Liprin-βs (β1, 2) and KazrinE. Drosophila and Xenopus also have three types of Liprins: Liprin-α, β, and γ. KazrinE and Liprin-γ have been recently identified as a third type of protein related to the Liprin family.25-28 Among four isoforms of Kazrin (KazrinA, B, C and E) only KazrinE contains the Liprin-α homology domain.27 In mammals, Liprin-α1, Liprin-β1 and β2 are expressed ubiquitously, whereas, Liprin-α2 and α3 are mainly expressed in the brain, and Liprin-α4 is in the brain, heart and skeletal muscle.25 In contrast, C. elegans contains only one Liprin-α, called syd-2 (synapse defective-2), which shares 50% identity to human Liprin-α1.

Bottom Line: Mammalian homolog of Diaphanous (mDia) is one of the Rho effectors and produces unbranched actin filaments.In our recent paper, we identified Liprin-α as an mDia interacting protein and found that Liprin-α negatively regulates the activity of mDia in the cell by displacing it from the plasma membrane through binding to the DID-DD region of mDia.Here, we review these findings and discuss how Liprin-α regulates the Rho-mDia pathway and how the mDia-Liprin-α complex functions in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology; Kyoto University Graduate School of Medicine; Kyoto, Japan.

ABSTRACT
Regulation of the actin cytoskeleton is crucial for cell morphology and migration. One of the key molecules that regulates actin remodeling is the small GTPase Rho. Rho shuttles between the inactive GDP-bound form and the active GTP-bound form, and works as a molecular switch in actin remodeling in response to both extra- and intra-cellular stimuli. Mammalian homolog of Diaphanous (mDia) is one of the Rho effectors and produces unbranched actin filaments. While Rho GTPases activate mDia, the mechanisms of how the activity of mDia is downregulated in cells remains largely unknown. In our recent paper, we identified Liprin-α as an mDia interacting protein and found that Liprin-α negatively regulates the activity of mDia in the cell by displacing it from the plasma membrane through binding to the DID-DD region of mDia. Here, we review these findings and discuss how Liprin-α regulates the Rho-mDia pathway and how the mDia-Liprin-α complex functions in vivo.

No MeSH data available.