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Antony Boucard: Adhesion GPCRs and the Molecular Code of Synapse Formation

Adhesion GPCRs represent one of the most architecturally complex and least understood branches of the GPCR superfamily. Characterized by extracellular domains exceeding 1,000 amino acids, autoproteolytic cleavage at the membrane, and a near-total absence of characterized ligands, these receptors long resisted the molecular tools that made classical family A GPCRs tractable. Only recently has the field established, with confidence, that adhesion GPCRs couple to G proteins at all.

Boucard's laboratory at UNAM in Mexico City sits at this frontier. His research centers on the molecular code governing synapse formation — how adhesion GPCRs, working alongside classical cell adhesion molecules, determine which neuronal partners recognize each other and which synaptic contacts stabilize. The work connects receptor biology to neuropsychiatric disease: addiction, autism spectrum disorder, schizophrenia, bipolar disorder, and cancer. The foundation of this program rests on a serendipitous discovery Boucard made in Thomas Südhof's lab — that a cell adhesion molecule and a GPCR, studied separately for over a decade, both bind alpha-latrotoxin from black widow spider venom, and that together they form an intercellular complex no one had previously described.

For Boucard, adhesion GPCRs are not simply a research subject. They are the place where everything he has cared about — biochemistry, cell communication, disease, and the students other institutions overlooked — finally came together.

About the Guest

Antony Boucard is a biochemist and cell biologist who leads the Boucard Laboratory at the National Autonomous University of Mexico (UNAM) in Mexico City, where he has built one of the only research programs in Latin America focused on adhesion GPCRs.

He completed graduate training in biochemistry at the Université de Sherbrooke and his postdoctoral fellowship in the laboratory of Thomas Südhof at UT Southwestern and Stanford University, where he made the initial observation linking cell adhesion molecules and GPCRs through their shared binding to alpha-latrotoxin.

His current research programs span synapse formation, addiction, autism, schizophrenia, bipolar disorder, and tumorigenesis, applying cell biology, BRET and FRET assays, microscopy, flow cytometry, and custom protein engineering approaches to probe adhesion GPCR function across physiological and pathological contexts.

Scientific Themes of the Conversation

Adhesion GPCRs as a distinct receptor class — autoproteolytic architecture, orphan status, and the long-delayed confirmation of G protein coupling
The molecular logic of synapse formation and how adhesion molecules encode synaptic specificity in the brain
Alpha-latrotoxin from black widow spider venom as an experimental bridge connecting cell adhesion molecules and GPCRs
Neuropsychiatric disease through the lens of adhesion GPCR biology — addiction, autism spectrum disorder, schizophrenia, and cancer
The structural bottleneck: what cryo-EM cannot yet capture about receptor dynamics at the cell surface
Pioneering a research field in an underrepresented scientific ecosystem, and recruiting from communities elite institutions have historically overlooked

Key Insights from the Conversation

1. Adhesion GPCRs Were Not Considered Real GPCRs

For decades, adhesion GPCRs were assigned to the GPCR superfamily on the basis of their seven-transmembrane topology alone — not because G protein coupling had been demonstrated. Whether they functionally coupled to G proteins remained genuinely open, and for much of the field's history, skepticism was reasonable. Boucard's work on their signaling capacity in the context of synaptic biology sits at this still-resolving frontier, where the biology is catching up to the structural classification.

2. A Forgotten Sample, a First Paper

During his graduate studies, Boucard left an enzymatic reaction on his bench over a weekend — called away for army training — and returned to find results that had eluded the lab for months. He nearly discarded the sample. Running it on instinct, he obtained reproducible data that became his first publication. The pattern established there — outcomes shaped as much by openness as by design — has followed him through every phase of his career since.

3. The Black Widow Toxin Nobody Put Together

Working in Südhof's lab on cell adhesion molecules, Boucard made a lateral decision: to test whether one of the proteins he was studying might bind to a GPCR he had no reason to investigate. The interaction was real. On a colleague's suggestion, he recognized that both proteins had independently been shown to bind alpha-latrotoxin from black widow spider venom — but no one had ever asked whether they interacted with each other. They formed an intercellular adhesion complex. Südhof himself was skeptical; the field had studied both proteins for over a decade without making the connection. That discovery became the foundation of Boucard's independent research program.

4. Adhesion GPCRs Open a Pandora's Box

Adhesion GPCRs appear across nearly every biological process — from embryonic development to synaptic maturation, from immune cell trafficking to tumorigenesis. Boucard describes this breadth not as an opportunity but as a constraint: the challenge for his lab has been choosing which processes to study rigorously rather than chasing the full landscape. Anchoring the work in synapse formation provides a tractable and biologically meaningful lens, while the transversal logic — that what is learned about adhesion in one context often illuminates another — keeps the research portfolio coherent.

5. The Structural Bottleneck

Cryo-EM has transformed understanding of classical GPCR structure, but adhesion GPCRs remain dramatically underrepresented in the structural database. The deeper issue, Boucard argues, is not just the quantity of structures but their nature: every cryo-EM image is a frozen moment, capturing a receptor in one state, in one membrane environment, at one point in time. What the field still cannot do is observe the dynamics of receptor assembly, complex formation, and signaling in real time at the cell surface. That gap is where the most important biology is happening.

6. Choosing Mexico City as a Scientific Bet

After postdoctoral and faculty positions at Stanford and UT Southwestern, Boucard surveyed the conventional research markets — North America, Western Europe — and concluded that his skills were not especially scarce there. Mexico City offered something different: a research territory in adhesion GPCR biology that was entirely unoccupied, a massive university drawing students from across Latin America and indigenous communities within Mexico, and a scientific culture where his particular combination of biochemistry, cell biology, and translational thinking could do something that wasn't already being done. Eight years in, he has not reconsidered the decision.

Episode Timeline

Timestamps were generated with AI assistance from the episode transcript and may not reflect exact segment boundaries. Use them as navigational guides.

00:00 Sponsor intro — GeneTex & Eurofins DiscoverX
00:43 Introducing Boucard: a scientific path that was never planned
01:40 From biochemistry by accident: Sherbrooke, Dallas, Stanford, Mexico City
03:43 The summer lab that changed everything — and why he turned down medical school
10:23 Army service, social work in Nicaragua, and the civil war that reframed resources and risk
16:18 Turning down the medical school acceptance — 25 years of no regrets
22:10 Université de Sherbrooke's industry-integrated curriculum and what it modeled about flexibility
26:06 Surviving crisis in Haiti and what scarcity teaches about choice
31:33 The underground restaurant in San Francisco, born out of an immigration emergency — and Chef's Table Season 2
43:45 Time, focus, and the discipline of 15 minutes a day
52:38 Why Mexico City: building a lab for students no one else was recruiting
01:00:00 Adhesion GPCRs — the receptor family that kept calling him back
01:04:58 The black widow toxin discovery — two proteins, 15 years of prior research, one untested pair
01:06:18 Why adhesion GPCRs are among the hardest receptors to work with, and why structures are finally coming
01:09:10 Synapse formation, addiction, autism, schizophrenia, and cancer: the lab's research logic
01:13:45 Assays: BRET, FRET, microscopy, flow cytometry, and engineering membrane-anchored ligands into solution
01:19:29 The dream tool — a nanoscale camera navigating the cell surface in real time
01:22:24 Advice to junior scientists: don't be afraid to be afraid
01:26:00 Three aha moments: socks, a forgotten sample, and one cold email to a Nobel laureate
01:35:33 Lab openings and where to find the Boucard Lab

Selected Quotes

"Every single one of my days right now has been just to reconstruct what I learned the day before. That's something that I really love — you kind of put yourself in the mindset of the kid once again."

"A lot of people say there's a lot of reasons not to do an experiment. There's a ton. But sometimes you can just do one. And you never know."

"I can't believe you won the Nobel Prize. Because at home, he can't even pick up his own socks." — Said to Boucard by a fellow Nobel laureate's wife, at a ceremony at Stanford, following the 2013 prize announcement

"If you willingly put yourself in a situation where you're willing to take risks, things will fall into place. But if you never try, you might not know. And whether you're there for a short time or for the rest of your life, you'll have the best time of your life during the time you're doing it."

About Dr. Antony A. Boucard Jr.

Dr. Antony Boucard joined the Université de Sherbrooke (Québec, Canada) as a B.S. student of the Biochemistry program in 1994 from which he graduated in 1997. It is then that his interest bloomed for the study of GPCRs while joining the group of Dr. Richard Leduc and Dr. Gaetan Guillemette in the Pharmacology department at the Université de Sherbrooke. He completed a master’s degree in 2000 and a Ph.D. degree in 2003 with a particular interest in the cardiovascular system by investigating the structure of the Angiotensin and Urotensin receptors through various biochemical approaches centered in the elucidation of ligand binding pocket determinants.

Motivated by a new ambition to study the nervous system, Dr. Boucard pursued postdoctoral training at the University of Texas Southwestern Medical Center in Dallas where he joined the group of Dr. Thomas Südhof. In this institution dear to the heart of GPCR enthusiasts given that its faculty personnel included Dr. Alfred Gilman, Nobel Laureate for his discovery of G proteins, Dr. Boucard ventured into the field of synaptic adhesion molecules which would eventually prompt him to investigate the role of a peculiar family of GPCRs belonging to the Adhesion subgroup. After a relocation to Stanford University where he pioneered work on ligand discovery for then orphan adhesion GPCRs, Dr. Boucard moved to Mexico City to establish himself as an independent investigator integrating the department of Cell Biology at the Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN).

Dr. Boucard´s lab focuses on molecular and cellular mechanisms underlying the function of adhesion GPCRs in the formation of synapses. Having a particular interest for a three-member family named latrophilins, his lab seeks to decipher the molecular code instructing adhesion events mediated by these GPCRs. The pharmacology of latrophilins brings about a great deal of challenges given that they are highly polymorphic proteins expressed as various alternatively spliced isoforms thus potentially resulting in differential modulation of cell signaling pathways. His lab highlighted the importance of splicing events in biasing latrophilins’ regulation of cyclic AMP pathways and for determining the magnitude of ligand selectivity. Additionally, his team is also interested in understanding the pathophysiological relevance of latrophilins’ function in neuropsychiatric disorders given their association with genetic susceptibility to the neurodevelopmental disorder known as attention deficit hyperactivity disorder (ADHD) but also to a comorbid clinical manifestation linked to addiction.

He also actively volunteers as an Associate Professor of the non-governmental organization Institut des Sciences, des Technologies et des Etudes Avancées d’Haïti (ISTEAH) to help consolidate higher education in Haiti.

Dr. Antony A. Boucard Jr. on the web