Apoptotic Cleavage of Rabaptin-5-like Proteins and a Model for Rabaptin-5 Inactivation in Apoptosis

Korobko, Elena V.; Palgova, Irina V.; Kiselev, Sergey L.; Коробко, И. В.

doi:10.4161/cc.5.16.3092

Cited by 7 publications

(6 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3A). The deletion in Rbpt5Δ4/2 indeed overlaps with a second reported Rab5-interacting segment (residues 216-318; Korobko et al, 2006) that might be inactivated by the deletion in Rbpt5Δ4/2. Expression of Rbpt5δ, a natural splice variant lacking residues 187-226, which hardly cut into the Rab5-interacting segment, did not cause endosome enlargement (Fig.…”

Section: Rab4 Is Required For Rbpt5 Recruitment Through Two Distinct mentioning

confidence: 98%

“…It was initially isolated as an interactor of Rab5 (Stenmark et al, 1995). It specifically binds Rab5-GTP through a C-terminal domain (residues 814-862; Vitale et al, 1998;Zhu et al, 2004b), but yeast two-hybrid and glutathione-S-transferase (GST)-Rab5 pulldown experiments have also observed some interaction through a second site in the N-terminal part of the protein (Deneka et al, 2003;Vitale et al, 1998), specifically in the segment 216-318 (Korobko et al, 2006). In addition, Rbpt5 associates, through its CC2-1 coiled-coil segment, to Rabex5 (also known as RABGEF1), the GEF of Rab5 (Horiuchi et al, 1997;Mattera et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome maturation

Kälin

Hirschmann

Buser

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

Rab GTPases control membrane identity, fusion and transport by interaction with effector proteins. Effectors that influence the activation-inactivation cycle of their own or other Rab proteins contribute to the timely conversion of Rab membrane identities. Rab5 and its effector rabaptin5 (Rbpt5, also known as RABEP1) are generally considered the prime example for a positive-feedback loop in which Rab5-GTP recruits Rbpt5 in complex with Rabex5 (also known as RABGEF1), the GDP/GTP exchange factor of Rab5, to early endosomes, thus maintaining the Rab5 membrane identity. By deletion analysis, we found that the membrane recruitment of Rabaptin5 required binding to Rab4 and Rabex5, but not Rab5. Deletion of either one of the two Rab5-binding domains or silencing of Rab5 expression did not affect Rabaptin5 recruitment, but produced giant endosomes with early and late endosomal characteristics. The results contradict the model of feedback activation of Rab5 and instead indicate that Rbpt5 is recruited by both Rabex5 recognizing ubiquitylated cargo and by Rab4 to activate Rab5 in a feed-forward manner.

show abstract

Section: Rab4 Is Required For Rbpt5 Recruitment Through Two Distinct mentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome maturation

Kälin

Hirschmann

Buser

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Rabaptin-5 cleavage has been proposed as a mechanism that can disrupt the endosome compartment during apoptosis. [47][48][49] Although we found no differences in the viability of mast cells in standard culture media, Rabaptin-5-deficient BMCMCs were more susceptible to apoptosis after growth factor withdrawal ( Figure S8). Future studies will be required to characterize in detail Rabaptin-5's role in cell survival.…”

Section: Discussionmentioning

confidence: 78%

Rabaptin-5 regulates receptor expression and functional activation in mast cells

Rios

Piliponsky

et al. 2008

Blood

View full text Add to dashboard Cite

Rab5 is a small GTPase that regulates early endocytic events and is activated by RabGEF1/Rabex-5. Rabaptin-5, a Rab5 interacting protein, was identified as a protein critical for potentiating RabGEF1/ Rabex-5's activation of Rab5. Using Rabaptin-5 shRNA knockdown, we show that Rabaptin-5 is dispensable for Rab5-dependent processes in intact mast cells, IntroductionMast cells are best known for their critical roles in immunoglobulin E (IgE)-associated immediate hypersensitivity reactions and other allergic disorders. [1][2][3][4] IgE primes the mast cell to undergo Agdependent activation by binding to the high-affinity IgE receptor (Fc⑀RI), a member of the immune receptor superfamily, 1-4 and multivalent Ag initiates mast cell activation by cross-linking 2 or more Fc⑀RI-bound IgE molecules that bind to that Ag. Mast cell activation induces a variety of responses, including the release of preformed pro-inflammatory mediators (eg, histamine, ␤-hexosaminidase) from the cytoplasmic granules, as well as the secretion of lipid mediators, cytokines, chemokines and growth factors. [1][2][3][4] Regulation of the expression of receptors and their downstream signaling pathways is critical for a cell to properly interpret and respond to the surrounding environment. Perturbations in these processes can have diverse and dramatic effects. 5 Receptor regulation is particularly important for mounting optimal responses to low concentrations of ligands, such as migration in response to chemotactic factors 6 or activation of secretion by Ags. 3,7 Mast cells in particular are well known for being able to respond to small amounts of Ags. [1][2][3][4] Although many proteins have been identified that modulate receptor traffic to and from the cell surface, members of the Rab family of small GTPases have emerged as major regulators of many of these membrane trafficking events. [8][9][10][11] Like all GTPases, Rabs cycle between GDP and GTP bound conformations, with the state of nucleotide binding dictating whether the Rab protein is active (GTP bound) or inactive (GDP bound). This nucleotide cycling is catalyzed by GEFs (guanine exchange factors; catalyze GTP binding) and GAPs (GTPase activating proteins; stimulate intrinsic GTPase activity of Rabs). Several of these Rab proteins have attracted much attention, including Rab5, the major regulator of early endocytic events, Rab4 and Rab11, regulators of recycling routes, and Rab7 and Rab9, regulators of the lysosomal pathway. 10 Despite intense studies of their biochemistry, the functions of these proteins in regulating the activation and signaling of intact cells have only recently been investigated. In mast cells, Rab27a and Rab27b and its effectors 12,13 regulate granule motility and degranulation, whereas the role of Rab3, initially reported to be important in regulating mast cell degranulaton, 14 remains to be fully clarified. 15 We have shown that RabGEF1/Rabex-5 (RabGEF1), a Rab5 GEF, is critical for regulating the activation of mouse bone marrow-derived cultured mast cells (BMCMCs)...

show abstract

“…18 A second Rab5 binding site was discovered in the N-terminal half of Rabaptin5 near CC1-2 by yeast 2-hybrid screening. 19 Furthermore, in vitro and in vivo studies identified binding sites for the GAT domain (domain found in GGAs and TOM1) of GGAs (Golgi-localized, g-ear-containing, ARF-binding proteins) and g-adaptin ear (GAE) domains of AP-1 and GGAs. 20 Their function was proposed to be the regulation of AP-1 or GGA dependent vesicle transport at endosomes.…”

Section: Feedforward Instead Of Feedback For Rab5 Activationmentioning

confidence: 99%

A fresh look at the function of Rabaptin5 on endosomes

2016

View full text Add to dashboard Cite

Apoptotic Cleavage of Rabaptin-5-like Proteins and a Model for Rabaptin-5 Inactivation in Apoptosis

Cited by 7 publications

References 18 publications

Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome maturation

Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome maturation

Rabaptin-5 regulates receptor expression and functional activation in mast cells

A fresh look at the function of Rabaptin5 on endosomes

Contact Info

Product

Resources

About