CAST2: identification and characterization of a protein structurally related to the presynaptic cytomatrix protein CAST

Deguchi-Tawarada, Maki; Inoue, Eiji; Takao-Rikitsu, Etsuko; Inoue, Marie; Ohtsuka, Toshihisa; Takai, Yoshimi

doi:10.1111/j.1356-9597.2004.00697.x

Cited by 84 publications

(125 citation statements)

References 24 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…N-terminal dimerization of ELKS causes the ELKS-RET chimeric protein to oligomerize and act as an oncoprotein, leading to papillary thyroid carcinoma (Nakata et al, 2002). ELKS has since been identified as a Rab6A-interacting and -regulating protein (Monier et al, 2002), as a member of the IB kinase (IKK) complex involved in NF-B signaling (Ducut Sigala et al, 2004), and as a member of the active zone complex in the mammalian nervous system (Ohtsuka et al, 2002;Wang et al, 2002;Deguchi-Tawarada et al, 2004). The role of ELKS in the nervous system is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…1, available at www.jneurosci.org as supplemental material). Mammalian ELKS isoforms directly interact with and colocalize with mammalian RIM at the active zone (Wang et al, 1997Ohtsuka et al, 2002;Deguchi-Tawarada et al, 2004). The localization of RIM at the active zone is conserved in C. elegans (Koushika et al, 2001).…”

Section: Rim and Elks Are Interacting Active Zone Proteins In C Elegansmentioning

confidence: 99%

“…In the cultured neuron system, RIM localization requires an interaction between the postsynaptic density-25/Discs large/zona occludens (PDZ)-binding motif at the C-terminal tail of ELKS and the RIM PDZ domain (Ohtsuka et al, 2002). However, these studies are difficult to interpret, because the ELKS and RIM transgenes are being overexpressed in a system that already contains native ELKS and RIM, both of which are expressed from more than one gene and as multiple different isoforms Johnson et al, 2003;Wang and Sudhof, 2003;Deguchi-Tawarada et al, 2004). Using C. elegans genetics, we generated animals that lack ELKS protein expression, examined ELKS involvement in synaptic transmission, and determined its relationship with RIM in vivo.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Redundant Localization Mechanisms of RIM and ELKS inCaenorhabditis elegans

Deken¹,

Vincent²,

Hadwiger³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

Active zone proteins play a fundamental role in regulating neurotransmitter release and defining release sites. The functional roles of active zone components are beginning to be elucidated; however, the mechanisms of active zone protein localization are unknown. Studies have shown that glutamine, leucine, lysine, and serine-rich protein (ELKS), a recently defined member of the active zone complex, acts to localize the active zone protein Rab3a-interacting molecule (RIM) and regulates synaptic transmission in cultured neurons. Here, we test the function of ELKS in vivo. Like mammalian ELKS, Caenorhabditis elegans ELKS is an active zone protein that directly interacts with the postsynaptic density-25/Discs large/zona occludens (PDZ) domain of RIM. However, RIM protein localizes in the absence of ELKS and vice versa. In addition, elks mutants exhibit neither the behavioral nor the physiological defects associated with unc-10 RIM mutants, indicating that ELKS is not a critical component of the C. elegans release machinery. Interestingly, expression of the soluble PDZ domain of RIM disrupts ELKS active zone targeting, suggesting a tight association between the two proteins in vivo. RIM truncations containing only the PDZ and C2A domains target to release sites in an ELKS-dependent manner. Together, these data identify ELKS as a new member of the C. elegans active zone complex, define the role of ELKS in synaptic transmission, and characterize the relationship between ELKS and RIM in vivo. Furthermore, they demonstrate that multiple different protein-protein interactions redundantly anchor both ELKS and RIM to active zones and implicate novel proteins in the formation of the active zone.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Rim and Elks Are Interacting Active Zone Proteins In C Elegansmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Redundant Localization Mechanisms of RIM and ELKS inCaenorhabditis elegans

Deken¹,

Vincent²,

Hadwiger³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Here, we have identified the adaptor proteins ERC1 (ELKS/Rab6-interacting/CAST family member 1) (Hida and Ohtsuka, 2010;Südhof, 2012) and LL5 (Paranavitane et al, 2003;Kishi et al, 2005) as important co-players, with liprin-a1, in the regulation of tumor cell migration and invasion. The ERC family (Nakata et al, 1999;Monier et al, 2002;Deguchi-Tawarada et al, 2004) includes ERC2, and two ERC1 isoforms, the brainspecific ERC1b and the widely expressed ERC1a (ELKSe) (Wang et al, 2002). In neurons, ERC proteins cooperate with liprin-a in the assembly of functional presynaptic sites (Dai et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Liprin-α1, ERC1 and LL5 identify a polarized, dynamic compartment implicated in cell migration

Astro

Chiaretti

Magistrati

et al. 2014

Journal of Cell Science

121

View full text Add to dashboard Cite

BSTRACTCell migration during development and metastatic invasion requires the coordination of actin and adhesion dynamics to promote protrusive activity at the front of the cell. The knowledge of the molecular mechanisms required to achieve such coordination is fragmentary. Here, we identify a new functional complex that drives cell motility. ERC1a (an isoform of ERC1) and the LL5 proteins LL5a and LL5b (encoded by PHLDB1 and PHLDB2, respectively) are required, together with liprin-a1, for effective migration and tumor cell invasion, and do so by stabilizing the protrusive activity at the cell front. Depletion of either protein negatively affects invasion, migration on extracellular matrix, lamellipodial persistence and the internalization of active integrin b1 receptors needed for adhesion turnover at the front of the cell. Liprin-a1, ERC1a and LL5 also define new highly polarized and dynamic cytoplasmic structures uniquely localized near the protruding cell edge. Our results indicate that the functional complex and the associated structures described here represent an important mechanism to drive tumor cell migration.

show abstract

“…The ERC family of CAZ proteins contains two known members: ERC1/ELKS/Rab6IP2/CAST2 and ERC2/CAST1 (Nakata et al, 1999;Monier et al, 2002;Ohtsuka et al, 2002;Wang et al, 2002;Deguchi-Tawarada et al, 2004). ERC1 has two splice variants, ubiquitous ERC1a and brain-specific ERC1b, whereas no splice variants are known for the brain-specific ERC2.…”

Section: Introductionmentioning

confidence: 99%

Organization of the Presynaptic Active Zone by ERC2/CAST1-Dependent Clustering of the Tandem PDZ Protein Syntenin-1

Yoon²,

Piccoli

et al. 2006

J. Neurosci.

View full text Add to dashboard Cite

Presynaptic active zones contain a cytoskeletal matrix called the CAZ, which is thought to play a critical role in the regulation of active zone formation and neurotransmitter release. Recent studies have identified several CAZ components, but little is known about how they contribute to the molecular organization of active zones. Here, we report a novel PDZ [postsynaptic density-95/Discs large/zona occludens-1] interaction between the CAZ protein ERC2/CAST1 and the tandem PDZ protein syntenin-1, which is known to associate with diverse synaptic proteins, including glutamate receptor subunits, SynCAM, and ␤-neurexin. This interaction promotes the localization of syntenin-1 at presynaptic ERC2 clusters. In addition to the PDZ interaction, multimerization of both ERC2 and syntenin-1 mediates syntenin-1 clustering. These results suggest that ERC2 promotes presynaptic syntenin-1 clustering by two distinct mechanisms and that syntenin-1 may contribute to the molecular organization of active zones by linking ERC2 and other CAZ components to diverse syntenin-1-associated synaptic proteins.

show abstract

CAST2: identification and characterization of a protein structurally related to the presynaptic cytomatrix protein CAST

Cited by 84 publications

References 24 publications

Redundant Localization Mechanisms of RIM and ELKS inCaenorhabditis elegans

Redundant Localization Mechanisms of RIM and ELKS inCaenorhabditis elegans

Liprin-α1, ERC1 and LL5 identify a polarized, dynamic compartment implicated in cell migration

Organization of the Presynaptic Active Zone by ERC2/CAST1-Dependent Clustering of the Tandem PDZ Protein Syntenin-1

Contact Info

Product

Resources

About