Heike Fölsch | Northwestern University Feinberg School of Medicine (original) (raw)

Papers by Heike Fölsch

Research paper thumbnail of Faculty Opinions recommendation of Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Sep 14, 2017

Research paper thumbnail of Faculty Opinions recommendation of Polarization-dependent selective transport to the apical membrane by KIF5B in MDCK cells

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Oct 23, 2007

Research paper thumbnail of Faculty Opinions recommendation of Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Nov 18, 2002

Research paper thumbnail of Faculty Opinions recommendation of Kinetic studies of the Arf activator Arno on model membranes in the presence of Arf effectors suggest control by a positive feedback loop

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Apr 19, 2011

Research paper thumbnail of Faculty Opinions recommendation of GPI-anchored proteins are directly targeted to the apical surface in fully polarized MDCK cells

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Apr 3, 2006

Research paper thumbnail of Faculty Opinions recommendation of Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Feb 5, 2007

Research paper thumbnail of Faculty Opinions recommendation of Differential involvement of endocytic compartments in the biosynthetic traffic of apical proteins

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Nov 18, 2008

Newly synthesized basolateral markers can traverse recycling endosomes en route to the surface of... more Newly synthesized basolateral markers can traverse recycling endosomes en route to the surface of Madin-Darby canine kidney cells; however, the routes used by apical proteins are less clear. Here, we functionally inactivated subsets of endocytic compartments and examined the effect on surface delivery of the basolateral marker vesicular stomatitis virus glycoprotein (VSV-G), the raft-associated apical marker influenza hemagglutinin (HA), and the non-raft-associated protein endolyn. Inactivation of transferrin-positive endosomes after internalization of horseradish peroxidase (HRP)-containing conjugates inhibited VSV-G delivery, but did not disrupt apical delivery. In contrast, inhibition of protein export from apical recycling endosomes upon expression of dominant-negative constructs of myosin Vb or Sec15 selectively perturbed apical delivery of endolyn. Ablation of apical endocytic components accessible to HRP-conjugated wheat germ agglutinin (WGA) disrupted delivery of HA but not endolyn. However, delivery of glycosylphosphatidylinositolanchored endolyn was inhibited by 450% under these conditions, suggesting that the biosynthetic itinerary of a protein is dependent on its targeting mechanism. Our studies demonstrate that apical and basolateral proteins traverse distinct endocytic intermediates en route to the cell surface, and that multiple routes exist for delivery of newly synthesized apical proteins.

Research paper thumbnail of Faculty Opinions recommendation of Lkb1 regulates organogenesis and early oncogenesis along AMPK-dependent and -independent pathways

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Mar 13, 2013

Research paper thumbnail of Faculty Opinions recommendation of Myosin VI is required for sorting of AP-1B-dependent cargo to the basolateral domain in polarized MDCK cells

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Apr 5, 2007

Research paper thumbnail of Faculty Opinions recommendation of Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Aug 13, 2003

Research paper thumbnail of Faculty Opinions recommendation of Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Apr 10, 2005

Research paper thumbnail of Faculty of 1000 evaluation for Induction of lateral lumens through disruption of a monoleucine-based basolateral-sorting motif in betacellulin

F1000 - Post-publication peer review of the biomedical literature, 2015

Research paper thumbnail of Faculty of 1000 evaluation for Microtubule motors mediate endosomal sorting by maintaining functional domain organization

F1000 - Post-publication peer review of the biomedical literature, 2013

Research paper thumbnail of Faculty of 1000 evaluation for Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination

F1000 - Post-publication peer review of the biomedical literature, 2007

Research paper thumbnail of Faculty of 1000 evaluation for Myosin V transports secretory vesicles via a Rab GTPase cascade and interaction with the exocyst complex

F1000 - Post-publication peer review of the biomedical literature, 2012

Research paper thumbnail of Faculty of 1000 evaluation for Yip3 catalyses the dissociation of endosomal Rab-GDI complexes

F1000 - Post-publication peer review of the biomedical literature, 2003

Research paper thumbnail of Faculty Opinions recommendation of PH-domain-dependent selective transport of p75 by kinesin-3 family motors in non-polarized MDCK cells

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, May 6, 2010

Research paper thumbnail of Faculty Opinions recommendation of A role for Yip1p in COPII vesicle biogenesis

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Oct 29, 2003

east Ypt1p-interacting protein (Yip1p) belongs to a conserved family of transmembrane proteins th... more east Ypt1p-interacting protein (Yip1p) belongs to a conserved family of transmembrane proteins that interact with Rab GTPases. We encountered Yip1p as a constituent of ER-derived transport vesicles, leading us to hypothesize a direct role for this protein in transport through the early secretory pathway. Using a cell-free assay that recapitulates protein transport from the ER to the Golgi complex, we find that affinity-purified antibodies directed against the hydrophilic amino terminus of Yip1p potently inhibit transport. Surprisingly, inhibition is specific to the COPII-dependent budding stage. In support of this in vitro Y observation, strains bearing the temperature-sensitive yip1-4 allele accumulate ER membranes at a nonpermissive temperature, with no apparent accumulation of vesicle intermediates. Genetic interaction analyses of the yip1-4 mutation corroborate a function in ER budding. Finally, ordering experiments show that preincubation of ER membranes with COPII proteins decreases sensitivity to anti-Yip1p antibodies, indicating an early requirement for Yip1p in vesicle formation. We propose that Yip1p has a previously unappreciated role in COPII vesicle biogenesis.

Research paper thumbnail of Faculty Opinions recommendation of Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Jul 28, 2004

fndosome-to-Golgi retrieval of the mannose 6-phosphate receptor (MPR) is required for lysosome bi... more fndosome-to-Golgi retrieval of the mannose 6-phosphate receptor (MPR) is required for lysosome biogenesis. Currently, this pathway is poorly understood. Analyses in yeast identified a complex of proteins called "retromer" that is essential for endosome-to-Golgi retrieval of the carboxypeptidase Y receptor Vps10p. Retromer comprises five distinct proteins: Vps35p, 29p, 26p, 17p, and 5p, which are conserved in mammals. Here, we show that retromer is required for the efficient retrieval of the cationindependent MPR (CI-MPR). Cells lacking mammalian E VPS26 fail to retrieve the CI-MPR, resulting in either rapid degradation of or mislocalization to the plasma membrane. We have localized mVPS26 to multivesicular body endosomes by electron microscopy, and through the use of CD8 reporter protein constructs have examined the effect of loss of mVPS26 upon the trafficking of membrane proteins that cycle between the endosome and the Golgi. The data presented here support the hypothesis that retromer performs a selective function in endosome-to-Golgi transport, mediating retrieval of the CI-MPR, but not furin.

Research paper thumbnail of Faculty Opinions recommendation of Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Jan 15, 2003

Cargo transfer from trans-Golgi network (TGN)derived transport carriers to endosomes involves a s... more Cargo transfer from trans-Golgi network (TGN)derived transport carriers to endosomes involves a still unde®ned set of tethering/fusion events. Here we analyze a molecular interaction that may play a role in this process. We demonstrate that the GGAs, a family of Arf-dependent clathrin adaptors involved in selection of TGN cargo, interact with the Rabaptin-5±Rabex-5 complex, a Rab4/Rab5 effector regulating endosome fusion. These interactions are bipartite: GGA-GAE domains recognize an FGPLV sequence (residues 439±443) in a predicted random coil of Rabaptin-5 (a sequence also recognized by the g1and g2-adaptin ears), while GGA-GAT domains bind to the C-terminal coiled-coils of Rabaptin-5. The GGA±Rabaptin-5 interaction decreases binding of clathrin to the GGA-hinge domain, and expression of green¯uorescent protein (GFP)±Rabaptin-5 shifts the localization of endogenous GGA1 and associated cargo to enlarged early endosomes. These observations thus identify a binding sequence for GAE/gadaptin ear domains and reveal a functional link between proteins regulating TGN cargo export and endosomal tethering/fusion events.

Research paper thumbnail of Faculty Opinions recommendation of Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Sep 14, 2017

Research paper thumbnail of Faculty Opinions recommendation of Polarization-dependent selective transport to the apical membrane by KIF5B in MDCK cells

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Oct 23, 2007

Research paper thumbnail of Faculty Opinions recommendation of Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Nov 18, 2002

Research paper thumbnail of Faculty Opinions recommendation of Kinetic studies of the Arf activator Arno on model membranes in the presence of Arf effectors suggest control by a positive feedback loop

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Apr 19, 2011

Research paper thumbnail of Faculty Opinions recommendation of GPI-anchored proteins are directly targeted to the apical surface in fully polarized MDCK cells

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Apr 3, 2006

Research paper thumbnail of Faculty Opinions recommendation of Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Feb 5, 2007

Research paper thumbnail of Faculty Opinions recommendation of Differential involvement of endocytic compartments in the biosynthetic traffic of apical proteins

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Nov 18, 2008

Newly synthesized basolateral markers can traverse recycling endosomes en route to the surface of... more Newly synthesized basolateral markers can traverse recycling endosomes en route to the surface of Madin-Darby canine kidney cells; however, the routes used by apical proteins are less clear. Here, we functionally inactivated subsets of endocytic compartments and examined the effect on surface delivery of the basolateral marker vesicular stomatitis virus glycoprotein (VSV-G), the raft-associated apical marker influenza hemagglutinin (HA), and the non-raft-associated protein endolyn. Inactivation of transferrin-positive endosomes after internalization of horseradish peroxidase (HRP)-containing conjugates inhibited VSV-G delivery, but did not disrupt apical delivery. In contrast, inhibition of protein export from apical recycling endosomes upon expression of dominant-negative constructs of myosin Vb or Sec15 selectively perturbed apical delivery of endolyn. Ablation of apical endocytic components accessible to HRP-conjugated wheat germ agglutinin (WGA) disrupted delivery of HA but not endolyn. However, delivery of glycosylphosphatidylinositolanchored endolyn was inhibited by 450% under these conditions, suggesting that the biosynthetic itinerary of a protein is dependent on its targeting mechanism. Our studies demonstrate that apical and basolateral proteins traverse distinct endocytic intermediates en route to the cell surface, and that multiple routes exist for delivery of newly synthesized apical proteins.

Research paper thumbnail of Faculty Opinions recommendation of Lkb1 regulates organogenesis and early oncogenesis along AMPK-dependent and -independent pathways

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Mar 13, 2013

Research paper thumbnail of Faculty Opinions recommendation of Myosin VI is required for sorting of AP-1B-dependent cargo to the basolateral domain in polarized MDCK cells

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Apr 5, 2007

Research paper thumbnail of Faculty Opinions recommendation of Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Aug 13, 2003

Research paper thumbnail of Faculty Opinions recommendation of Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Apr 10, 2005

Research paper thumbnail of Faculty of 1000 evaluation for Induction of lateral lumens through disruption of a monoleucine-based basolateral-sorting motif in betacellulin

F1000 - Post-publication peer review of the biomedical literature, 2015

Research paper thumbnail of Faculty of 1000 evaluation for Microtubule motors mediate endosomal sorting by maintaining functional domain organization

F1000 - Post-publication peer review of the biomedical literature, 2013

Research paper thumbnail of Faculty of 1000 evaluation for Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination

F1000 - Post-publication peer review of the biomedical literature, 2007

Research paper thumbnail of Faculty of 1000 evaluation for Myosin V transports secretory vesicles via a Rab GTPase cascade and interaction with the exocyst complex

F1000 - Post-publication peer review of the biomedical literature, 2012

Research paper thumbnail of Faculty of 1000 evaluation for Yip3 catalyses the dissociation of endosomal Rab-GDI complexes

F1000 - Post-publication peer review of the biomedical literature, 2003

Research paper thumbnail of Faculty Opinions recommendation of PH-domain-dependent selective transport of p75 by kinesin-3 family motors in non-polarized MDCK cells

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, May 6, 2010

Research paper thumbnail of Faculty Opinions recommendation of A role for Yip1p in COPII vesicle biogenesis

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Oct 29, 2003

east Ypt1p-interacting protein (Yip1p) belongs to a conserved family of transmembrane proteins th... more east Ypt1p-interacting protein (Yip1p) belongs to a conserved family of transmembrane proteins that interact with Rab GTPases. We encountered Yip1p as a constituent of ER-derived transport vesicles, leading us to hypothesize a direct role for this protein in transport through the early secretory pathway. Using a cell-free assay that recapitulates protein transport from the ER to the Golgi complex, we find that affinity-purified antibodies directed against the hydrophilic amino terminus of Yip1p potently inhibit transport. Surprisingly, inhibition is specific to the COPII-dependent budding stage. In support of this in vitro Y observation, strains bearing the temperature-sensitive yip1-4 allele accumulate ER membranes at a nonpermissive temperature, with no apparent accumulation of vesicle intermediates. Genetic interaction analyses of the yip1-4 mutation corroborate a function in ER budding. Finally, ordering experiments show that preincubation of ER membranes with COPII proteins decreases sensitivity to anti-Yip1p antibodies, indicating an early requirement for Yip1p in vesicle formation. We propose that Yip1p has a previously unappreciated role in COPII vesicle biogenesis.

Research paper thumbnail of Faculty Opinions recommendation of Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Jul 28, 2004

fndosome-to-Golgi retrieval of the mannose 6-phosphate receptor (MPR) is required for lysosome bi... more fndosome-to-Golgi retrieval of the mannose 6-phosphate receptor (MPR) is required for lysosome biogenesis. Currently, this pathway is poorly understood. Analyses in yeast identified a complex of proteins called "retromer" that is essential for endosome-to-Golgi retrieval of the carboxypeptidase Y receptor Vps10p. Retromer comprises five distinct proteins: Vps35p, 29p, 26p, 17p, and 5p, which are conserved in mammals. Here, we show that retromer is required for the efficient retrieval of the cationindependent MPR (CI-MPR). Cells lacking mammalian E VPS26 fail to retrieve the CI-MPR, resulting in either rapid degradation of or mislocalization to the plasma membrane. We have localized mVPS26 to multivesicular body endosomes by electron microscopy, and through the use of CD8 reporter protein constructs have examined the effect of loss of mVPS26 upon the trafficking of membrane proteins that cycle between the endosome and the Golgi. The data presented here support the hypothesis that retromer performs a selective function in endosome-to-Golgi transport, mediating retrieval of the CI-MPR, but not furin.

Research paper thumbnail of Faculty Opinions recommendation of Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Jan 15, 2003

Cargo transfer from trans-Golgi network (TGN)derived transport carriers to endosomes involves a s... more Cargo transfer from trans-Golgi network (TGN)derived transport carriers to endosomes involves a still unde®ned set of tethering/fusion events. Here we analyze a molecular interaction that may play a role in this process. We demonstrate that the GGAs, a family of Arf-dependent clathrin adaptors involved in selection of TGN cargo, interact with the Rabaptin-5±Rabex-5 complex, a Rab4/Rab5 effector regulating endosome fusion. These interactions are bipartite: GGA-GAE domains recognize an FGPLV sequence (residues 439±443) in a predicted random coil of Rabaptin-5 (a sequence also recognized by the g1and g2-adaptin ears), while GGA-GAT domains bind to the C-terminal coiled-coils of Rabaptin-5. The GGA±Rabaptin-5 interaction decreases binding of clathrin to the GGA-hinge domain, and expression of green¯uorescent protein (GFP)±Rabaptin-5 shifts the localization of endogenous GGA1 and associated cargo to enlarged early endosomes. These observations thus identify a binding sequence for GAE/gadaptin ear domains and reveal a functional link between proteins regulating TGN cargo export and endosomal tethering/fusion events.