About

Peter Novick is a Professor of Cellular and Molecular Medicine at UC San Diego, with a research focus on the molecular mechanisms of membrane traffic, particularly as they relate to cell polarity. His lab studies the structure and inheritance of the endoplasmic reticulum, exploring how membrane trafficking is coordinated through rab GEF and GAP cascades. Novick's work has contributed to understanding the regulation of membrane traffic by Rab GTPases, the role of exocyst subunits in plasma membrane function, and the processes involved in ER autophagy and inheritance. His research has advanced knowledge of the molecular interactions that govern membrane dynamics, cell polarity, and organelle inheritance, with significant contributions to the fields of cell biology and biochemistry.

Research topics

• Biology
• Chemistry
• Cell biology
• Biochemistry
• Genetics

Selected publications

• Different ER–plasma membrane tethers play opposing roles in autophagy of the cortical ER

  Proceedings of the National Academy of Sciences · 2024-06-05 · 5 citations

  articleOpen accessSenior authorCorresponding

  The endoplasmic reticulum (ER) undergoes degradation by selective macroautophagy (ER-phagy) in response to starvation or the accumulation of misfolded proteins within its lumen. In yeast, actin assembly at sites of contact between the cortical ER (cER) and endocytic pits acts to displace elements of the ER from their association with the plasma membrane (PM) so they can interact with the autophagosome assembly machinery near the vacuole. A collection of proteins tether the cER to the PM. Of these, Scs2/22 and Ist2 are required for cER-phagy, most likely through their roles in lipid transport, while deletion of the tricalbins, TCB1 / 2 /3, bypasses those requirements. An artificial ER–PM tether blocks cER-phagy in both the wild type (WT) and a strain lacking endogenous tethers, supporting the importance of cER displacement from the PM. Scs2 and Ist2 can be cross-linked to the selective cER-phagy receptor, Atg40. The COPII cargo adaptor subunit, Lst1, associates with Atg40 and is required for cER-phagy. This requirement is also bypassed by deletion of the ER–PM tethers, suggesting a role for Lst1 prior to the displacement of the cER from the PM during cER-phagy. Although pexophagy and mitophagy also require actin assembly, deletion of ER–PM tethers does not bypass those requirements. We propose that within the context of rapamycin-induced cER-phagy, Scs2/22, Ist2, and Lst1 promote the local displacement of an element of the cER from the cortex, while Tcb1/2/3 act in opposition, anchoring the cER to the plasma membrane.

  PublisherOA PDFDOI

• Exploring the consequences of redirecting an exocytic Rab onto endocytic vesicles

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-02-10

  preprintOpen accessSenior authorCorresponding

  Bidirectional vesicular traffic links compartments along the exocytic and endocytic pathways. Rab GTPases have been implicated in specifying the direction of vesicular transport because anterograde vesicles are marked with a different Rab than retrograde vesicles. To explore this proposal, we sought to redirect an exocytic Rab, Sec4, onto endocytic vesicles by fusing the catalytic domain of the Sec4 GEF, Sec2, onto the CUE localization domain of Vps9, a GEF for the endocytic Rab, Ypt51. The Sec2GEF-GFP-CUE construct was found to localize to bright puncta predominantly near sites of polarized growth and this localization was strongly dependent upon the ability of the CUE domain to bind to the ubiquitin moieties added to the cytoplasmic tails of proteins destined for endocytic internalization. Sec4 and Sec4 effectors were recruited to these puncta with varying efficiency. The puncta appeared to consist of clusters of 80 nm vesicles and although the puncta are largely static, FRAP analysis suggests that traffic into and out of these clusters continues. Cells expressing Sec2GEF-GFP-CUE grew surprisingly well and secreted protein at near normal efficiency, implying that Golgi derived secretory vesicles were delivered to polarized sites of cell growth, where they tethered and fused with the plasma membrane despite the misdirection of Sec4 and its effectors. In total, the results suggest that while Rabs play a critical role in regulating vesicular transport, cells are remarkably tolerant of Rab misdirection.

  PublisherOA PDFDOI

• Exploring the consequences of redirecting an exocytic Rab onto endocytic vesicles

  Molecular Biology of the Cell · 2023-03-01

  articleOpen accessSenior author

  Bidirectional vesicular traffic links compartments along the exocytic and endocytic pathways. Rab GTPases have been implicated in specifying the direction of vesicular transport. To explore this possibility, we sought to redirect an exocytic Rab, Sec4, onto endocytic vesicles by fusing the catalytic domain of the Sec4 GEF, Sec2, onto the CUE localization domain of Vps9, a GEF for the endocytic Rab Ypt51. The Sec2GEF-GFP-CUE construct localized to bright puncta predominantly near sites of polarized growth, and this localization was dependent on the ability of the CUE domain to bind to the ubiquitin moieties added to the cytoplasmic tails of proteins destined for endocytic internalization. Sec4 and Sec4 effectors were recruited to these puncta with various efficiencies. Cells expressing Sec2GEF-GFP-CUE grew surprisingly well and secreted protein at near-normal efficiency, implying that Golgi-derived secretory vesicles were delivered to polarized sites of cell growth despite the misdirection of Sec4 and its effectors. A low efficiency mechanism for localization of Sec2 to secretory vesicles that is independent of known cues might be responsible. In total, the results suggest that while Rabs may play a critical role in specifying the direction of vesicular transport, cells are remarkably tolerant of Rab misdirection.

  PublisherOA PDFDOI

• Autophagy of the ER Requires Actin Assembly Driven by the Interaction of ER with Endocytic Pits

  Contact · 2022-01-01

  articleOpen access1st authorCorresponding

  Autophagy of the cortical ER in budding yeast was unexpectedly found to require End3, a component of the endocytic machinery that promotes the assembly of actin at endocytic pits on the plasma membrane. The cortical ER transiently interacts with invaginating endocytic pits through a linkage consisting of VAP proteins, oxysterol binding proteins and type I myosins. These proteins are required for actin assembly and for autophagy of the ER. Assembly of actin at these contact sites may direct the movement of ER away from the cortex towards sites of autophagosome assembly.

  PublisherDOI

• Double NPY motifs at the N-terminus of Sso2 synergistically bind Sec3 to promote membrane fusion

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-03-12

  preprintOpen accessCorresponding

  Abstract Exocytosis is an active vesicle trafficking process by which eukaryotes secrete materials to the extracellular environment and insert membrane proteins into the plasma membrane. The final step of exocytosis in yeast involves the assembly of two t-SNAREs, Sso1/2 and Sec9, with the v-SNARE, Snc1/2, on secretory vesicles. The rate-limiting step in this process is the formation of a binary complex of the two t-SNAREs. Despite a previous report of acceleration of binary complex assembly by Sec3, it remains unknown how Sso2 is efficiently recruited to the vesicle-docking site marked by Sec3. Here we report a crystal structure of the pleckstrin homology (PH) domain of Sec3 in complex with a nearly full-length version of Sso2 lacking only its C-terminal transmembrane helix. The structure shows a previously uncharacterized binding site for Sec3 at the N-terminus of Sso2, consisting of two highly conserved triple residue motifs (NPY: Asn-Pro-Tyr). We further reveal that the two NPY motifs bind Sec3 synergistically, which together with the previously reported binding interface constitute dual-site interactions between Sso2 and Sec3 to drive the fusion of secretory vesicles at target sites on the plasma membrane. Significance SNARE assembly, which involves one v-SNARE with two t-SNARE proteins, drives the fusion of vesicles to target compartments. The rate-limiting step in SNARE assembly is the assembly of the two t-SNARE proteins on the target membrane. Previous studies in yeast showed that Sec3, a component of the exocyst vesicle tethering complex, directly interacts with the t-SNARE protein Sso2 to promote fast assembly of an Sso2-Sec9 binary t-SNARE complex. This paper presents a new crystal structure of the Sec3 PH domain in complex with a nearly full-length version of Sso2, which reveals a previously unknown binding site for Sec3 at the N-terminus of Sso2. Our work demonstrates that the dual-site interactions between Sso2 and Sec3 plays an essential role in promoting the fusion of secretory vesicles at target sites on the plasma membrane.

  PublisherOA PDFDOI

• CHAPTER 3 The Holocaust Is Not— and Is Not Likely to Become— a Global Memory

  Berghahn Books · 2022-10-29

  book-chapter1st authorCorresponding
  PublisherDOI

• Actin assembly at sites of contact between the cortical ER and endocytic pits promotes ER autophagy

  Autophagy · 2022-05-09 · 2 citations

  articleOpen accessSenior authorCorresponding

  deletion library implicated End3 in autophagy of the endoplasmic reticulum (ER). Together with Pan1, End3 coordinates endocytic site initiation with the localized assembly of branching actin filaments that promotes invagination of endocytic pits. Oxysterol binding proteins function as an inter-organelle bridge by interacting with VAP proteins on the cortical ER and type I myosins on the endocytic pit. These proteins not only promote localized actin assembly at contact sites, they are required for ER autophagy as well. We propose that localized actin polymerization can push the edge of an ER sheet from the cell cortex toward the site of autophagosome assembly near the vacuole.

  PublisherOA PDFDOI

• Double NPY motifs at the N-terminus of the yeast t-SNARE Sso2 synergistically bind Sec3 to promote membrane fusion

  eLife · 2022 · 12 citations

  • Cell biology
  • Biology
  • Chemistry

  Exocytosis is an active vesicle trafficking process by which eukaryotes secrete materials to the extracellular environment and insert membrane proteins into the plasma membrane. The final step of exocytosis in yeast involves the assembly of two t-SNAREs, Sso1/2 and Sec9, with the v-SNARE, Snc1/2, on secretory vesicles. The rate-limiting step in this process is the formation of a binary complex of the two t-SNAREs. Despite a previous report of acceleration of binary complex assembly by Sec3, it remains unknown how Sso2 is efficiently recruited to the vesicle-docking site marked by Sec3. Here, we report a crystal structure of the pleckstrin homology (PH) domain of Sec3 in complex with a nearly full-length version of Sso2 lacking only its C-terminal transmembrane helix. The structure shows a previously uncharacterized binding site for Sec3 at the N-terminus of Sso2, consisting of two highly conserved triple residue motifs (NPY: Asn-Pro-Tyr). We further reveal that the two NPY motifs bind Sec3 synergistically, which together with the previously reported binding interface constitute dual-site interactions between Sso2 and Sec3 to drive the fusion of secretory vesicles at target sites on the plasma membrane.

  PublisherDOI

• Author Reply to Peer Reviews of Double NPY motifs at the N-terminus of Sso2 synergistically bind Sec3 to promote membrane fusion

  2022-07-20

  peer-review
  PublisherDOI

• Author response: Double NPY motifs at the N-terminus of the yeast t-SNARE Sso2 synergistically bind Sec3 to promote membrane fusion

  2022-07-29

  peer-reviewOpen access
  PublisherDOI

Recent grants

• Coordination of membrane traffic through rab GEF and GAP cascades

  NIH · $4.4M · 2008–2021

• NIH Grant R01GM073892

  NIH · $1.4M · 2010

• NIH Grant P01CA046128

  NIH · $29.7M · 2007

• NIH Grant R37GM035370

  NIH · $3.9M · 2011

• Genetics of secretion in yeast

  NIH · $9.9M · 1985–2028

Frequent coauthors

• Susan Ferro‐Novick

  University of California, San Diego

  43 shared

• Patrick Brennwald

  University of North Carolina at Chapel Hill

  25 shared

• Michelle D. Garrett

  University of Kent

  22 shared

• Wei Guo

  14 shared

• Fern P. Finger

  Rensselaer Polytechnic Institute

  13 shared

• Ruth Collins

  Cornell University

  12 shared

• Yunrui Du

  Howard Hughes Medical Institute

  12 shared

• Adam S. Lauring

  New York Proton Center

  11 shared