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Pre-metazoan origins and evolution of the cadherin adhesome.

Murray PS, Zaidel-Bar R - Biol Open (2014)

Bottom Line: We found that the transition to multicellularity was accompanied by the appearance of a small number of adaptor proteins, and we show how these proteins may have helped to integrate pre-metazoan sub-networks via PDZ domain-peptide interactions.Finally, we found the increase in network complexity in higher metazoans to have been driven primarily by expansion of paralogs.In summary, our analysis helps to explain how the complex protein network associated with cadherin at adherens junctions first came together in the first metazoan and how it evolved into the even more complex mammalian cadhesome.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA Center of Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, Irving Cancer Research Center, New York, NY 10032, USA.

No MeSH data available.


Related in: MedlinePlus

Evolutionary age of cadhesome components.Proteins and protein families of the “simplified” cadhesome are colored according to when in evolution they appeared, and organized based on how they interact with the “classical” cadherin–catenin “core” (central semi-circle). Protein age is distinguished by color: unikont origin or older (red), opisthokont (orange), holozoa (yellow), metazoan (green), eumetazoa (cyan), and bilateria/vertebrata (violet). Some protein families are represented by one member of the family (LPP/++++), with each “+” signifying an additional family member. Components that interact directly with the cytoplasmic tail of cadherin or one of the catenins in vertebrates are located within “Shell 1”; components that interact indirectly with cadherin–catenin – i.e. via components in “Shell 1” – are located within “Shell 2”. All remaining components are located outside the two shells. Component types are distinguished by shape: adaptors (oval), regulatory proteins (rectangle), actin dynamics regulators (pentagon), cytoskeleton (hexagon), with receptors spanning the plasma membrane (and extracellular domains drawn to schematically show their domain structure). Cadhesome receptors are colored based on when in our analysis they appear as full membrane-spanning proteins with both cytoplasmic and extracellular domains. Boxed are components shared with other systems, including the spectrin–actin cytoskeleton, metazoan polarity complexes, and the integrin adhesome.
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f08: Evolutionary age of cadhesome components.Proteins and protein families of the “simplified” cadhesome are colored according to when in evolution they appeared, and organized based on how they interact with the “classical” cadherin–catenin “core” (central semi-circle). Protein age is distinguished by color: unikont origin or older (red), opisthokont (orange), holozoa (yellow), metazoan (green), eumetazoa (cyan), and bilateria/vertebrata (violet). Some protein families are represented by one member of the family (LPP/++++), with each “+” signifying an additional family member. Components that interact directly with the cytoplasmic tail of cadherin or one of the catenins in vertebrates are located within “Shell 1”; components that interact indirectly with cadherin–catenin – i.e. via components in “Shell 1” – are located within “Shell 2”. All remaining components are located outside the two shells. Component types are distinguished by shape: adaptors (oval), regulatory proteins (rectangle), actin dynamics regulators (pentagon), cytoskeleton (hexagon), with receptors spanning the plasma membrane (and extracellular domains drawn to schematically show their domain structure). Cadhesome receptors are colored based on when in our analysis they appear as full membrane-spanning proteins with both cytoplasmic and extracellular domains. Boxed are components shared with other systems, including the spectrin–actin cytoskeleton, metazoan polarity complexes, and the integrin adhesome.

Mentions: Many studies have demonstrated that AJs are more than simply the cadherin–catenin “core”. Searching the literature, we previously found over 170 proteins reported to be associated with the “core”. We call this network of proteins and their interactions the cadhesome (Zaidel-Bar, 2013). To determine when in evolution cadhesome proteins first appeared we first clustered similar proteins into families, yielding the “simplified” cadhesome, and then determined in what phyla a representative of each family first appeared (Fig. 4). This is depicted in graphical form in Fig. 8, where evolutionary age is color-coded, function is shape-coded, and position is a function of whether the human protein interacts directly or indirectly with the “core”. As evident in Fig. 8, protein families with pre-metazoa origins (colored red, orange, and yellow) make up ∼70% of this “simplified” cadhesome, and many of these interact with the “core” (innermost shell). That so many ancient proteins interact with the “core” directly (“shell 1”), coupled with the pre-metazoa origins of the catenins, seems to suggest that much of the AJ regulatory network may have been in place prior to metazoa. This helps to explain how the transition from uni- to multicellular life forms could take place, but it also elicits important questions: for example, what was the function of cadhesome proteins before AJs existed? How were so many pre-existing proteins and networks incorporated and integrated by so few novel proteins?


Pre-metazoan origins and evolution of the cadherin adhesome.

Murray PS, Zaidel-Bar R - Biol Open (2014)

Evolutionary age of cadhesome components.Proteins and protein families of the “simplified” cadhesome are colored according to when in evolution they appeared, and organized based on how they interact with the “classical” cadherin–catenin “core” (central semi-circle). Protein age is distinguished by color: unikont origin or older (red), opisthokont (orange), holozoa (yellow), metazoan (green), eumetazoa (cyan), and bilateria/vertebrata (violet). Some protein families are represented by one member of the family (LPP/++++), with each “+” signifying an additional family member. Components that interact directly with the cytoplasmic tail of cadherin or one of the catenins in vertebrates are located within “Shell 1”; components that interact indirectly with cadherin–catenin – i.e. via components in “Shell 1” – are located within “Shell 2”. All remaining components are located outside the two shells. Component types are distinguished by shape: adaptors (oval), regulatory proteins (rectangle), actin dynamics regulators (pentagon), cytoskeleton (hexagon), with receptors spanning the plasma membrane (and extracellular domains drawn to schematically show their domain structure). Cadhesome receptors are colored based on when in our analysis they appear as full membrane-spanning proteins with both cytoplasmic and extracellular domains. Boxed are components shared with other systems, including the spectrin–actin cytoskeleton, metazoan polarity complexes, and the integrin adhesome.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4265756&req=5

f08: Evolutionary age of cadhesome components.Proteins and protein families of the “simplified” cadhesome are colored according to when in evolution they appeared, and organized based on how they interact with the “classical” cadherin–catenin “core” (central semi-circle). Protein age is distinguished by color: unikont origin or older (red), opisthokont (orange), holozoa (yellow), metazoan (green), eumetazoa (cyan), and bilateria/vertebrata (violet). Some protein families are represented by one member of the family (LPP/++++), with each “+” signifying an additional family member. Components that interact directly with the cytoplasmic tail of cadherin or one of the catenins in vertebrates are located within “Shell 1”; components that interact indirectly with cadherin–catenin – i.e. via components in “Shell 1” – are located within “Shell 2”. All remaining components are located outside the two shells. Component types are distinguished by shape: adaptors (oval), regulatory proteins (rectangle), actin dynamics regulators (pentagon), cytoskeleton (hexagon), with receptors spanning the plasma membrane (and extracellular domains drawn to schematically show their domain structure). Cadhesome receptors are colored based on when in our analysis they appear as full membrane-spanning proteins with both cytoplasmic and extracellular domains. Boxed are components shared with other systems, including the spectrin–actin cytoskeleton, metazoan polarity complexes, and the integrin adhesome.
Mentions: Many studies have demonstrated that AJs are more than simply the cadherin–catenin “core”. Searching the literature, we previously found over 170 proteins reported to be associated with the “core”. We call this network of proteins and their interactions the cadhesome (Zaidel-Bar, 2013). To determine when in evolution cadhesome proteins first appeared we first clustered similar proteins into families, yielding the “simplified” cadhesome, and then determined in what phyla a representative of each family first appeared (Fig. 4). This is depicted in graphical form in Fig. 8, where evolutionary age is color-coded, function is shape-coded, and position is a function of whether the human protein interacts directly or indirectly with the “core”. As evident in Fig. 8, protein families with pre-metazoa origins (colored red, orange, and yellow) make up ∼70% of this “simplified” cadhesome, and many of these interact with the “core” (innermost shell). That so many ancient proteins interact with the “core” directly (“shell 1”), coupled with the pre-metazoa origins of the catenins, seems to suggest that much of the AJ regulatory network may have been in place prior to metazoa. This helps to explain how the transition from uni- to multicellular life forms could take place, but it also elicits important questions: for example, what was the function of cadhesome proteins before AJs existed? How were so many pre-existing proteins and networks incorporated and integrated by so few novel proteins?

Bottom Line: We found that the transition to multicellularity was accompanied by the appearance of a small number of adaptor proteins, and we show how these proteins may have helped to integrate pre-metazoan sub-networks via PDZ domain-peptide interactions.Finally, we found the increase in network complexity in higher metazoans to have been driven primarily by expansion of paralogs.In summary, our analysis helps to explain how the complex protein network associated with cadherin at adherens junctions first came together in the first metazoan and how it evolved into the even more complex mammalian cadhesome.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA Center of Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, Irving Cancer Research Center, New York, NY 10032, USA.

No MeSH data available.


Related in: MedlinePlus