Cdc15 is an essential F-BAR (Fer/CIP4 homology-BAR) domain protein in Schizosaccharomyces pombe that serves as the founding member of the PCH (Pombe Cdc15 Homology) protein family. It is a critical scaffold linking the cytokinetic contractile ring (CR) to the plasma membrane during cell division.
Cdc15 is one of the earliest and most abundant CR proteins to arrive at the division site PMID:7634333. It forms the membrane-proximal layer of the CR (0-80 nm from PM), linking the plasma membrane to internal CR components [PMID:28914606, PMID:33357436]. The F-BAR domain oligomerizes to create a membrane-bound platform, and when oligomerization is disrupted, the CR is unstable and can disassemble PMID:33357436. The SH3 domain extends ~150 nm from the PM in the mature CR and interacts with a network of proteins ensuring robust cytokinesis PMID:33357436.
Cdc15 directly recruits the formin Cdc12 to the cell middle through binding between the Cdc15 F-BAR domain and a conserved N-terminal motif (aa 24-36) in Cdc12, with a dissociation constant of 1.1 nM PMID:25688133. Loss of this interaction reduces Cdc12, F-actin, and actin-binding proteins at the CR by ~35%, delays CR formation by ~25%, and is synthetically lethal with mutations in the alternative Cdc12 recruitment pathway (Rng2/Myo2) PMID:25688133. Cdc15 also recruits Arp2/3 complex activator Myo1p for the second actin nucleation pathway PMID:12939254.
Cdc15 is hyperphosphorylated in interphase, which generates a closed, inactive conformation that prevents membrane binding, oligomerization, and partner interactions PMID:32101481. Dephosphorylation at mitotic onset activates Cdc15, allowing it to oligomerize, bind membranes, and scaffold the CR. Multiple kinases regulate Cdc15:
- Pom1 (DYRK kinase): Phosphorylates 22 sites on Cdc15, preventing membrane binding and Pxl1 interaction; this is key for preventing septum formation at cell tips (tip occlusion) PMID:32101481
- Cdk1: Phosphoinhibits the Cdc12-Cdc15 interaction, opposing CR formation until the appropriate cell cycle stage PMID:29343550
- Kin1: Phosphorylates Cdc15 on non-overlapping sites PMID:32101481
Cdc15 localizes to actin cortical patches during interphase and participates in endocytosis. At endocytic sites, Cdc15 assembles stoichiometrically with Myo1p and promotes Arp2/3-dependent actin polymerization. Cells depleted of Cdc15 assemble 3-5 fold less actin in patches and patches move shorter distances from the PM PMID:21885283.
Cdc15 contributes to establishment of bipolar cell polarity PMID:23093943. The DYRK kinase Pom1 phosphorylates Cdc15 at cell tips to prevent ectopic septum formation, ensuring medial division PMID:32101481. Cdc15 also promotes Cdc42 activation during cytokinesis and cell polarization through regulation of GEF Gef1.
Unlike some other BAR domain proteins, the Cdc15 F-BAR domain does NOT bend/tubulate membranes. Instead, oligomerization (not membrane bending) underlies its function in cytokinesis PMID:26702831.
| Partner | Interaction domain | Function |
|---|---|---|
| Cdc12 (formin) | F-BAR domain (cytosolic face) | Actin nucleation for CR |
| Myo1 (type I myosin) | F-BAR/coiled-coil region | Arp2/3 complex activation |
| Pxl1 (paxillin) | SH3 + IDR | CR integrity, calcineurin recruitment |
| Fic1 | SH3 domain | CR disassembly, septation |
| Imp2 | SH3 domain | CR function |
| Blt1 | Unknown | Node component |
| Rng2 (IQGAP) | Via SH3 network | CR constriction |
Also localizes to: mating projection tip during conjugation PMID:25825517, medial membrane band [PMID:15517003, PMID:31276301].