Monoclonal antibody to novel cell surface epitope on Hsc70 promotes morphogenesis of bile ducts in newborn rat liver

Mills, David; Haskell, Michelle D.; Callanan, Helen; Flanagan, Donna; Brilliant, Kate E.; Yang, Dongqin; Hixson, Douglas C.

doi:10.1007/s12192-009-0120-2

Cited by 11 publications

(11 citation statements)

References 51 publications

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“…This observation has been confirmed by others (De Maio 2011). Other hsp have also been detected within cellular membranes (Bausero et al 2004, Belles et al 1999, Roberts et al 1999, Mills et al 2010). Thus, Hsp70 presents an unorthodox capacity to get inserted into the lipid bilayer without any conventional transmembrane domains.…”

Section: Introductionsupporting

confidence: 60%

Bacterial Hsp70 (DnaK) and mammalian Hsp70 interact differently with lipid membranes

López¹,

Cauvi

Arispe

et al. 2016

Cell Stress and Chaperones

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The cellular response to stress is orchestrated by the expression of a family of proteins termed heat shock proteins (hsp) that are involved in the stabilization of basic cellular processes to preserve cell viability and homeostasis. The bulk of hsp function occurs within the cytosol and subcellular compartments. However, some hsp have also been found outside cells released by an active mechanism independent of cell death. Extracellular hsp act as signaling molecules directed at activating a systemic response to stress. The export of hsp requires the translocation from the cytosol into the extracellular milieu across the plasma membrane. We have proposed that membrane insertion is the initial step in this export process. We investigated the interaction of the major inducible hsp from mammalian (Hsp70) and bacterial (DnaK) species with liposomes. We found that mammalian Hsp70 displayed a high specificity for negatively charged phospholipids, such as phosphatidyl serine, whereas DnaK interacted with all lipids tested regardless of the charge. Both proteins were inserted into the lipid bilayer as demonstrated by resistance to acid or basic washes that was confirmed by partial protection from proteolytic cleavage. Several regions of mammalian Hsp70 were inserted into the membrane with a small portion of the N-terminus end exposed to the outer phase of the liposome. In contrast, the N-terminus end of DnaK was inserted into the membrane, exposing the C-terminus end outside the liposome. Mammalian Hsp70 was found to make high oligomeric complexes upon insertion into the membranes whereas DnaK only formed dimers within the lipid bilayer. These observations suggest that both Hsp70s interact with lipids, but mammalian Hsp70 displays a high degree of specificity and structure as compared with the bacterial form.

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Section: Introductionsupporting

confidence: 60%

Bacterial Hsp70 (DnaK) and mammalian Hsp70 interact differently with lipid membranes

López¹,

Cauvi

Arispe

et al. 2016

Cell Stress and Chaperones

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“…While HSC70 is typically considered to be a cytosolic protein, a small number of groups have reported the presence of HSC70 on the cell surface . In the absence of classical lipid binding or transmembrane domains, the cell surface orientation of HSC70 remains unclear.…”

Section: Resultsmentioning

confidence: 99%

“…HSC70 is structurally similar to all members of the HSP70 family, each of which contains an ATPase domain, a peptide binding domain that defines substrate specificity, and an EEVD C-terminal sequences that allows association with J-domain-containing co-chaperones [54]. HSC70 is best described as a molecular chaperone involved in disassembly of clathrin-coated vesicles [55], however HSC70 also plays a role in a number of other cellular functions including cell proliferation [56], cell signaling [57,58], differentiation [51], cell adhesion [58,59], migration [60], and cytokine-dependent cell survival [61]. Many of these functions are cell type-specific and mediated by the recruitment of HSC70 to specific subcellular structures by the association with different classes of cochaperones that utilise the ATP activity of HSC70 [54].…”

Section: Discussionmentioning

confidence: 99%

The Mesenchymal Precursor Cell Marker Antibody STRO-1 Binds to Cell Surface Heat Shock Cognate 70

et al. 2017

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Since its discovery more than 25 years ago, the STRO-1 antibody has played a fundamental role in defining the hierarchical nature of mesenchymal precursor cells (MPC) and their progeny. STRO-1 antibody binding remains a hallmark of immature pluripotent MPC. Despite the significance of STRO-1 in the MPC field, the identity of the antigen has remained elusive. Using a combination of two-dimensional gel electrophoresis, coupled with Western blotting and Tandem mass spectroscopy, we have identified the STRO-1 antigen as heat shock cognate 70 (HSC70;HSPA8). STRO-1 binds to immune-precipitated HSC70 and siRNA-mediated knock down of HSPA8 reduced STRO-1 binding. STRO-1 surface binding does not correlate with HSC70 expression and sequestration of cholesterol reduces STRO-1 surface binding, suggesting that the plasma membrane lipid composition may be an important determinant in the presentation of HSC70 on the cell surface. HSC70 is present on the surface of STRO-1 but not STRO-1 cell lines as assessed by cell surface biotinylation and recombinant HSC70 blocks STRO-1 binding to the cell surface. The STRO-1 epitope on HSC70 was mapped to the ATPase domain using a series of deletion mutants in combination with peptide arrays. Deletion of the first four amino acids of the consensus epitope negated STRO-1 binding. Notably, in addition to HSC70, STRO-1 cross-reacts with heat shock protein 70 (HSP70), however all the clonogenic cell activity is restricted to the STRO-1 /HSP70 fraction. These results provide important insight into the properties that define multipotent MPC and provide the impetus to explore the role of cell surface HSC70 in MPC biology. Stem Cells 2017;35:940-951.

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“…Indeed, the presence of other hsp on the cell surface has been widely shown by many investigators under different physiological and pathological conditions (42). The constitutive member of the cytosolic Hsp70 family, Hsc70 (HSPA8), was observed on the bile duct membrane (52). Grp78, also known as BIP, has been detected on the cell surface (53).…”

Section: The Export Of Hspmentioning

confidence: 99%

Extracellular Heat Shock Proteins

Maio¹,

Vázquez

2013

Shock

151

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The expression of heat shock proteins (hsp) is a basic and well conserved cellular response to an array of stresses. These proteins are involved in the repair of cellular damage induced by the stress, which is necessary for the salutary resolution from the insult. Moreover, they confer protection from subsequent insults, which has been coined stress tolerance. Since these proteins are expressed in subcellular compartments, it was thought that their function during stress conditions was circumscribed to the intracellular environment. However, it is now well established that hsp can also be present outside cells where they appear to display a function different than the well understood chaperone role. Extracellular hsp act as alert stress signals priming other cells, particularly of the immune system, to avoid the propagation of the insult and favor resolution. Since the majority of hsp do not possess a secretory peptide signal, they are likely be exported by a non-classical secretory pathway. Different mechanisms have been proposed to explain the export of hsp, including translocation across the plasma membrane and release associated with lipid vesicles, as well as the passive release after cell death by necrosis. Extracellular hsp appear in various flavors, including membrane-bound and membrane-free forms. All of these variants of extracellular hsp suggest that their interactions with cells may be quite diverse, both in target cell types and the activation signaling pathways. This review addresses some of our current knowledge about the release and relevance of extracellular hsp.

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Monoclonal antibody to novel cell surface epitope on Hsc70 promotes morphogenesis of bile ducts in newborn rat liver

Abstract: We previously described a cell surface reactive monoclonal antibody, MAb OC

Cited by 11 publications

References 51 publications

Bacterial Hsp70 (DnaK) and mammalian Hsp70 interact differently with lipid membranes

Bacterial Hsp70 (DnaK) and mammalian Hsp70 interact differently with lipid membranes

The Mesenchymal Precursor Cell Marker Antibody STRO-1 Binds to Cell Surface Heat Shock Cognate 70

Extracellular Heat Shock Proteins

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