Membrane Targeting of C2 Domains of Phospholipase C-δ Isoforms*

By Bharath Ananthanarayanan, Sudipto Das, S. Rhee, D. Murray, W. Cho. Journal of Biological Chemistry, 2002

84 citations recorded by the source corpus.

The C2 domain is a Ca2+-dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. To understand the mechanisms by which the C2 domain mediates the membrane targeting of PLC-δ isoforms, we measured the in vitro membrane binding of the C2 domains of PLC-δ1, -δ3, and -δ4 by surface plasmon resonance and monolayer techniques and their subcellular localization by time-lapse confocal microscopy. The membrane binding of the PLC-δ1-C2 is driven by nonspecific electrostatic interactions between the Ca2+-induced cationic surface of protein and the anionic membrane and specific interactions involving Ca2+, Asn647, and phosphatidylserine (PS). The PS selectivity of PLC-δ1-C2 governs its specific Ca2+-dependent subcellular targeting to the plasma membrane. The membrane binding of the PLC-δ3-C2 also involves Ca2+-induced nonspecific electrostatic interactions and PS coordination, and the latter leads to specific subcellular targeting to the plasma membrane. In contrast to PLC-δ1-C2 and PLC-δ3-C2, PLC-δ4-C2 has significant Ca2+-independent membrane affinity and no PS selectivity due to the presence of cationic residues in the Ca2+-binding loops and the substitution of Ser for the Ca2+-coordinating Asp in position 717. Consequently, PLC-δ4-C2 exhibits unique pre-localization to the plasma membrane prior to Ca2+ import and non-selective Ca2+-mediated targeting to various cellular membranes, suggesting that PLC-δ4 might have a novel regulatory mechanism. Together, these results establish the C2 domains of PLC-δ isoforms as Ca2+-dependent membrane targeting domains that have distinct membrane binding properties that control their subcellular localization behaviors.

Subfields: Cell Biology, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c65b5757a51d88f58586d7662e648b7f3fcf1fc0

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In Cell Biology

1. Andriy Kryshtafovych
2. John Moult
3. Krzysztof Fidelis
4. David T. Jones
5. Tanja Kortemme
6. D. Murray

In Genetics

1. Andriy Kryshtafovych
2. Andrej Sali
3. Krzysztof Fidelis
4. David T. Jones
5. Torsten Schwede
6. Ian A. Wilson
7. Rhiju Das
8. Adam Godzik

In Molecular Biology

1. Torsten Schwede
2. Andrej Sali
3. Yang Zhang
4. Ben M. Webb
5. Andriy Kryshtafovych
6. Krzysztof Fidelis
7. David Baker
8. Roland L. Dunbrack

Citations in the corpus

• Outcome of a Workshop on Applications of Protein Models in Biomedical Research (2009, background): “The construction of models of the membrane binding domains from different families (Ananthanarayanan et al., 2002; Blatner et al., 2004; Stahelin et al., 2004; Yu et al., 2004) also illustrates how homology modeling allows the identification of functional properties of proteins that are different th”
• Biology and Biochemistry of Plant Phospholipases (2011, background): “The C2 domain, in addition to potentially interacting with the EF hand domain, has been shown to be involved in targeting PI-PLCs to the plasma membrane after activation by calcium (Ananthanarayanan et al., 2002).”