Maxence Nachury, PhD

Professor

Ophthalmology

Address:

555 Mission Bay Blvd South, Rm 352X

UCSF Box 3120

San Francisco, CA 94158

United States

Phone:

Email:

UCSF Profiles

We study the primary cilium, a surface-exposed organelle required for vision, olfaction and developmental signaling. Our lab is interested in the mechanisms of trafficking in and out of cilia and how trafficking decisions impact signaling at the cilium. One research axis focuses on Bardet-Biedl Syndrome (BBS), a ciliopathy characterized by obesity, skeletal malformations and kidney cysts. The BBSome is an evolutionarily conserved complex of 8 BBS proteins that traffics signaling receptors out of cilia and we aim to decipher the molecular details of BBSome-mediated trafficking and the cellular, biochemical and structural level. A second research direction is aimed at cilia-derived extracellular vesicles (EVs). Ciliary signaling receptors that fail conventional exit are packaged into ciliary EVs. By dissecting the mechanisms of ciliary EV biogenesis, we will gain insight into the roles of these extracellular parcels in cell-cell communication.

Research Interests:

Trafficking biology of the primary cilium

Publications:

Tonic ubiquitination of the central body weight regulator melanocortin receptor 4 (MC4R) promotes its constitutive exit from cilia.

PLoS biology

Ojeda-Naharros I, Das T, Castro RA, Bazan JF, Vaisse C, Nachury MV

Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling.

Cell reports

Hoi KK, Xia W, Wei MM, Ulloa Navas MJ, Garcia Verdugo JM, Nachury MV, Reiter JF, Fancy SPJ

The ancestral ESCRT protein TOM1L2 selects ubiquitinated cargoes for retrieval from cilia.

Developmental cell

Shinde SR, Mick DU, Aoki E, Rodrigues RB, Gygi SP, Nachury MV

MRAP2 regulates energy homeostasis by promoting primary cilia localization of MC4R.

JCI insight

Bernard A, Ojeda Naharros I, Yue X, Mifsud F, Blake A, Bourgain-Guglielmetti F, Ciprin J, Zhang S, McDaid E, Kim K, Nachury MV, Reiter JF, Vaisse C

The gymnastics of intraflagellar transport complexes keeps trains running inside cilia.

Cell

Nachury MV

Shedding of ciliary vesicles at a glance.

Journal of cell science

Ojeda Naharros I, Nachury MV

Localization of GFP-Tagged Proteins Under the Electron Microscope.

Sara Gil-Perotin, A. Cebrián-Silla, V. Herranz-Pérez, P. García-Belda, S. Gil-García, M. Fil, J. S. Lee, M. V. Nachury, José Manuel García-Verdugo

Time-resolved proteomics profiling of the ciliary Hedgehog response.

The Journal of Cell Biology

May EA, Kalocsay M, D'Auriac IG, Schuster PS, Gygi SP, Nachury MV, Mick DU

Ubiquitin chains earmark GPCRs for BBSome-mediated removal from cilia.

The Journal of Cell Biology

Shinde SR, Nager AR, Nachury MV

Near-atomic structures of the BBSome reveal the basis for BBSome activation and binding to GPCR cargoes.

eLife

Yang S, Bahl K, Chou HT, Woodsmith J, Stelzl U, Walz T, Nachury MV

The Molecular Architecture of Native BBSome Obtained by an Integrated Structural Approach.

Structure (London, England : 1993)

Chou HT, Apelt L, Farrell DP, White SR, Woodsmith J, Svetlov V, Goldstein JS, Nager AR, Li Z, Muller J, Dollfus H, Nudler E, Stelzl U, DiMaio F, Nachury MV, Walz T

Establishing and regulating the composition of cilia for signal transduction.

Nature reviews. Molecular cell biology

Nachury MV, Mick DU

Effects of α-tubulin acetylation on microtubule structure and stability.

Proceedings of the National Academy of Sciences of the United States of America

Eshun-Wilson L, Zhang R, Portran D, Nachury MV, Toso DB, Löhr T, Vendruscolo M, Bonomi M, Fraser JS, Nogales E

The molecular machines that traffic signaling receptors into and out of cilia.

Current opinion in cell biology

Nachury MV

BBSome trains remove activated GPCRs from cilia by enabling passage through the transition zone.

The Journal of Cell Biology

Ye F, Nager AR, Nachury MV

A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies.

Nature genetics

Breslow DK, Hoogendoorn S, Kopp AR, Morgens DW, Vu BK, Kennedy MC, Han K, Li A, Hess GT, Bassik MC, Chen JK, Nachury MV

BORC Regulates the Axonal Transport of Synaptic Vesicle Precursors by Activating ARL-8.

Current biology : CB

Niwa S, Tao L, Lu SY, Liew GM, Feng W, Nachury MV, Shen K

Chemical structure-guided design of dynapyrazoles, cell-permeable dynein inhibitors with a unique mode of action.

eLife

Steinman JB, Santarossa CC, Miller RM, Yu LS, Serpinskaya AS, Furukawa H, Morimoto S, Tanaka Y, Nishitani M, Asano M, Zalyte R, Ondrus AE, Johnson AG, Ye F, Nachury MV, Fukase Y, Aso K, Foley MA, Gelfand VI, Chen JK, Carter AP, Kapoor TM

Microtubules acquire resistance from mechanical breakage through intralumenal acetylation.

Science (New York, N.Y.)

Xu Z, Schaedel L, Portran D, Aguilar A, Gaillard J, Marinkovich MP, Théry M, Nachury MV

Membrane traffic control by cytoskeletal and molecular machines.

Molecular biology of the cell

Lee TH, Nachury MV

Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes.

Journal of medical genetics

Bruel AL, Franco B, Duffourd Y, Thevenon J, Jego L, Lopez E, Deleuze JF, Doummar D, Giles RH, Johnson CA, Huynen MA, Chevrier V, Burglen L, Morleo M, Desguerres I, Pierquin G, Doray B, Gilbert-Dussardier B, Reversade B, Steichen-Gersdorf E, Baumann C, Panigrahi I, Fargeot-Espaliat A, Dieux A, David A, Goldenberg A, Bongers E, Gaillard D, Argente J, Aral B, Gigot N, St-Onge J, Birnbaum D, Phadke SR, Cormier-Daire V, Eguether T, Pazour GJ, Herranz-Pérez V, Goldstein JS, Pasquier L, Loget P, Saunier S, Mégarbané A, Rosnet O, Leroux MR, Wallingford JB, Blacque OE, Nachury MV, Attie-Bitach T, Rivière JB, Faivre L, Thauvin-Robinet C

Measurement of tubulin oligomers self-assembly by FRET.

Protocol Exchange

Didier Portran, Didier Portran, Maxence Nachury

Tubulin acetylation protects long-lived microtubules against mechanical ageing.

Nature cell biology

Portran D, Schaedel L, Xu Z, Théry M, Nachury MV

An Actin Network Dispatches Ciliary GPCRs into Extracellular Vesicles to Modulate Signaling.

Cell

Nager AR, Goldstein JS, Herranz-Pérez V, Portran D, Ye F, Garcia-Verdugo JM, Nachury MV

Abstract B068: Structural basis for Notch1 engagement of Delta-like 4 and Jagged1.

Immune Regulation of T Cell Responses/ Evolving Concepts in Cancer Immunology

Vincent C. Luca, Kevin M. Jude, Nathan W. Pierce, Maxence V. Nachury, Suzanne Fischer, K. Christopher Garcia

Localization of GFP-Tagged Proteins at the Electron Microscope.

Receptor and Ion Channel Detection in the Brain

Sara Gil-Perotin, A. Cebrián-Silla, V. Herranz-Pérez, P. García-Belda, S. Gil-García, M. Fil, J. S. Lee, M. V. Nachury, José Manuel García-Verdugo

Loss of the BBSome perturbs endocytic trafficking and disrupts virulence of Trypanosoma brucei.

Proceedings of the National Academy of Sciences of the United States of America

Langousis G, Shimogawa MM, Saada EA, Vashisht AA, Spreafico R, Nager AR, Barshop WD, Nachury MV, Wohlschlegel JA, Hill KL

The Intraflagellar Transport Protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3.

Cilia

G Liew, F Ye, A Nager, J Murphy, J Lee, M Aguiar, D Breslow, S Gygi, M Nachury

Proteomics of Primary Cilia by Proximity Labeling.

Developmental cell

Mick DU, Rodrigues RB, Leib RD, Adams CM, Chien AS, Gygi SP, Nachury MV

Cytoplasmic Dynein Antagonists with Improved Potency and Isoform Selectivity.

ACS chemical biology

See SK, Hoogendoorn S, Chung AH, Ye F, Steinman JB, Sakata-Kato T, Miller RM, Cupido T, Zalyte R, Carter AP, Nachury MV, Kapoor TM, Chen JK

Microtubules self-repair in response to mechanical stress.

Nature materials

Schaedel L, John K, Gaillard J, Nachury MV, Blanchoin L, Théry M

Structural biology. Structural basis for Notch1 engagement of Delta-like 4.

Science (New York, N.Y.)

Luca VC, Jude KM, Pierce NW, Nachury MV, Fischer S, Garcia KC

Analysis of soluble protein entry into primary cilia using semipermeabilized cells.

Methods in cell biology

Breslow DK, Nachury MV

Structural basis for membrane targeting of the BBSome by ARL6.

Nature structural & molecular biology

Mourão A, Nager AR, Nachury MV, Lorentzen E

The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3.

Developmental cell

Liew GM, Ye F, Nager AR, Murphy JP, Lee JS, Aguiar M, Breslow DK, Gygi SP, Nachury MV

How do cilia organize signalling cascades?

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

Nachury MV

The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation.

Nature genetics

Thauvin-Robinet C, Lee JS, Lopez E, Herranz-Pérez V, Shida T, Franco B, Jego L, Ye F, Pasquier L, Loget P, Gigot N, Aral B, Lopes CA, St-Onge J, Bruel AL, Thevenon J, González-Granero S, Alby C, Munnich A, Vekemans M, Huet F, Fry AM, Saunier S, Rivière JB, Attié-Bitach T, Garcia-Verdugo JM, Faivre L, Mégarbané A, Nachury MV

Α-tubulin K40 acetylation is required for contact inhibition of proliferation and cell-substrate adhesion.

Molecular biology of the cell

Aguilar A, Becker L, Tedeschi T, Heller S, Iomini C, Nachury MV

Movement of Signaling Receptors Inside Primary Cilia.

Biophysical Journal

Maxence Nachury

Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure.

Molecular biology of the cell

Howes SC, Alushin GM, Shida T, Nachury MV, Nogales E

Cilia grow by taking a bite out of the cell.

Developmental cell

Pierce NW, Nachury MV

An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier.

The Journal of Cell Biology

Breslow DK, Koslover EF, Seydel F, Spakowitz AJ, Nachury MV

αTAT1 catalyses microtubule acetylation at clathrin-coated pits.

Nature

Montagnac G, Meas-Yedid V, Irondelle M, Castro-Castro A, Franco M, Shida T, Nachury MV, Benmerah A, Olivo-Marin JC, Chavrier P

Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18).

Journal of medical genetics

Scheidecker S, Etard C, Pierce NW, Geoffroy V, Schaefer E, Muller J, Chennen K, Flori E, Pelletier V, Poch O, Marion V, Stoetzel C, Strähle U, Nachury MV, Dollfus H

Single molecule imaging reveals a major role for diffusion in the exploration of ciliary space by signaling receptors.

eLife

Ye F, Breslow DK, Koslover EF, Spakowitz AJ, Nelson WJ, Nachury MV

Structure of the α-tubulin acetyltransferase, αTAT1, and implications for tubulin-specific acetylation.

Proceedings of the National Academy of Sciences of the United States of America

Friedmann DR, Aguilar A, Fan J, Nachury MV, Marmorstein R

A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.

PLoS genetics

Seo S, Zhang Q, Bugge K, Breslow DK, Searby CC, Nachury MV, Sheffield VC

Give chance a chance.

Molecular biology of the cell

Nachury MV

Primary cilia: how to keep the riff-raff in the plasma membrane.

Current biology : CB

Breslow DK, Nachury MV

Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome.

Proceedings of the National Academy of Sciences of the United States of America

Westlake CJ, Baye LM, Nachury MV, Wright KJ, Ervin KE, Phu L, Chalouni C, Beck JS, Kirkpatrick DS, Slusarski DC, Sheffield VC, Scheller RH, Jackson PK

The END network couples spindle pole assembly to inhibition of the anaphase-promoting complex/cyclosome in early mitosis.

Developmental cell

Ban KH, Torres JZ, Miller JJ, Mikhailov A, Nachury MV, Tung JJ, Rieder CL, Jackson PK

Websites:

http://nachurylab.ucsf.edu/

Faculty Type:

Core CVRI Faculty

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Maxence Nachury, PhD