Kinectin Anchors the Translation Elongation Factor-1δ to the Endoplasmic Reticulum

Ong, Lawrence; Er, Connie P. N.; Ho, Alexandra; Aung, May; Yu, Hanry

doi:10.1074/jbc.m210917200

Cited by 31 publications

(32 citation statements)

References 47 publications

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“…The results of these functional assays confirm previous evidence (Ong et al, 2000;Ong et al, 2003) indicating that the essential kinesin-binding domain of human kinectin is in the region of residues 1188-1288 and lend strong support to the idea that ER assembly and morphogenesis is kinectindependent via its interaction with kinesin. 120 kDa kinectin is specifically associated with mitochondria and kinectin-kinesin interaction influences mitochondria dynamics In chicken and human, at least two different forms of kinectin have been observed, the 160 kDa species and a shorter, Nterminally truncated version of 120 kDa.…”

Section: Kinectin-kinesin Interaction Is Important For Er Extensionsupporting

confidence: 80%

“…It also points to the possibility that kinectin may bind non-motor partners through binding domains residing outside the conventional kinesin binding motif or through non proteinprotein interactions, such as lipid attachments to membranes. Recent evidence substantiates this possibility by demonstrating with genetic, in vivo and biophysical methods the interaction of a kinectin isoform with translation elongation factor 1δ subunit (Ong et al, 2003). This kinectin isoform lacks a large portion of the kinesin-binding domain.…”

Section: Discussionmentioning

confidence: 72%

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Distribution and functions of kinectin isoforms

Santama

Ong

et al. 2004

Journal of Cell Science

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Kinectin is an integral transmembrane protein on the endoplasmic reticulum, binding to kinesin, interacting with Rho GTPase and anchoring the translation elongation factor-1 complex. There has been debate on the specific role(s) of kinectin in different species and cell types. Here we identified 15 novel kinectin isoforms in the mouse nervous system, constituting a family of alternatively spliced carboxyl-terminal variants. Isoform expression is subject to cell type- and developmental stage-specific regulation. We raised specific antibodies to the kinectin variants to characterise their differential intracellular localisation and discovered that certain kinectin isoforms are found in axons where kinectin was previously believed to be absent. We also demonstrated in vivo by overexpression and RNA interference assay that kinectin is selectively involved in the transport of specific types of organelles. A 160 kDa kinectin species is mainly concentrated in the endoplasmic reticulum, anchored via its transmembrane domain and is essential for endoplasmic reticulum membrane extension. A 120 kDa kinectin species is specifically associated with mitochondria, and its interaction with kinesin was found to influence mitochondrial dynamics. These findings contribute to a more unified view of kinectin function. They suggest that different cellular processes use specific kinectin isoforms to mediate intracellular motility and targeting by transient interaction with different motor proteins or other binding partners.

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Section: Kinectin-kinesin Interaction Is Important For Er Extensionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 72%

Distribution and functions of kinectin isoforms

Santama

Ong

et al. 2004

Journal of Cell Science

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“…The kinectin gene is not found in Caenorhabditis elegans or Drosophila genomes, where conserved conventional kinesin heavy chain gene is present (13). Furthermore, kinectin isoforms without vd3 or vd4 have indeed been identified in cells (7,9,10), implying that the kinectin isoforms lacking either vd3 or vd4 (overlapping the kinesin-binding domain) cannot serve as the membrane anchors for kinesin (10). These findings suggest that kinectin should have additional or alternative functions other than interacting with kinesin for organelle motility.…”

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confidence: 81%

Kinectin-dependent Assembly of Translation Elongation Factor-1 Complex on Endoplasmic Reticulum Regulates Protein Synthesis

Ong

Lin

Zhang

et al. 2006

Journal of Biological Chemistry

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Kinectin is an integral membrane protein with many isoforms primarily found on the endoplasmic reticulum. It has been found to bind kinesin, Rho GTPase, and translation elongation factor-1␦. None of the existing models for the quaternary organization of the elongation factor-1 complex in higher eukaryotes involves kinectin. We have investigated here the assembly of the elongation factor-1 complex onto endoplasmic reticulum via kinectin using in vitro and in vivo assays. We established that the entire elongation factor-1 complex can be anchored to endoplasmic reticulum via kinectin, and the interacting partners are as follows. Kinectin binds EF-1␦, which in turn binds EF-1␥ but not EF-1␤; EF-1␥ binds EF-1␦ and EF-1␤ but not kinectin. In vivo splice blocking of the kinectin exons 36 and 37 produced kinectin lacking the EF-1␦ binding domain, which disrupted the membrane localization of EF-1␦, EF-1␥, and EF-1␤ on endoplasmic reticulum, similar to the disruptions seen with the overexpression of kinectin fragments containing the EF-1␦ binding domain. The disruptions of the EF-1␦/kinectin interaction inhibited expression of membrane proteins but enhanced synthesis of cytosolic proteins in vivo. These findings suggest that anchoring the elongation factor-1 complex onto endoplasmic reticulum via EF-1␦/kinectin interaction is important for regulating protein synthesis in eukaryotic cells.

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“…In addition to kinesin-1 binding, kinectin also binds to elongation factor-1δ and a number of small G-proteins (Alberts et al, 1998;Hotta et al, 1996;Ong et al, 2003;Vignal et al, 2001). Elongation factor-1δ, which is involved in protein synthesis, has not been shown to have any effect on cell migration, although elongation factor-1 has been implicated in cancer cell invasion (Pecorari et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Kinectin-dependent ER transport supports the focal complex maturation required for chemotaxis in shallow gradients

Pawijit

Teo

et al. 2016

Journal of Cell Science

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Chemotaxis in shallow gradients of chemoattractants is accomplished by preferential maintenance of protrusions oriented towards the chemoattractant; however, the mechanism of preferential maintenance is not known. Here, we test the hypothesis that kinectindependent endoplasmic reticulum (ER) transport supports focal complex maturation to preferentially maintain correctly oriented protrusions. We knocked down kinectin expression in MDA-MB-231 cells using small interfering RNA and observed that kinectin contributes to the directional bias, but not the speed, of cell migration. Kymograph analysis revealed that the extension of protrusions oriented towards the chemoattractant was not affected by kinectin knockdown, but that their maintenance was. Immunofluorescence staining and live-cell imaging demonstrated that kinectin transports ER preferentially to protrusions oriented towards the chemoattractant. ER then promotes the maturation of focal complexes into focal adhesions to maintain these protrusions for chemotaxis. Our results show that kinectin-dependent ER distribution can be localized by chemoattractants and provide a mechanism for biased protrusion choices during chemotaxis in shallow gradients of chemoattractants.

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Kinectin Anchors the Translation Elongation Factor-1δ to the Endoplasmic Reticulum

Cited by 31 publications

References 47 publications

Distribution and functions of kinectin isoforms

Distribution and functions of kinectin isoforms

Kinectin-dependent Assembly of Translation Elongation Factor-1 Complex on Endoplasmic Reticulum Regulates Protein Synthesis

Kinectin-dependent ER transport supports the focal complex maturation required for chemotaxis in shallow gradients

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