About

Professor Margot E. Quinlan obtained her B.A. at Reed College in 1991 and spent two years conducting research at the University of Erlangen-Nurnberg in Germany. She earned her Ph.D. from the University of Pennsylvania in 2002, working with Yale Goldman. Following her doctoral studies, she was a postdoctoral fellow at UCSF with Dyche Mullins until 2008. In 2008, she joined the faculty in the Department of Chemistry and Biochemistry at UCLA. Her research focuses on using biochemistry, microscopy, and genetic approaches to study the dynamics of the actin cytoskeleton, particularly the roles of proteins Spire and Cappuccino in building actin networks essential for early body axis development in Drosophila. Her work aims to understand how these proteins collaborate, regulate cell polarity, and their potential roles in mammalian disease contexts.

Research topics

• Cell biology
• Biology
• Chemistry
• Biophysics
• Optics

Selected publications

• The Cappuccino interactome reveals an intracellular role for Semaphorin-2a in Drosophila oogenesis

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-14

  articleOpen accessSenior authorCorresponding

  The spatiotemporal regulation of an actin mesh during Drosophila oogenesis is essential for proper localization of cell polarity determinants that establish the future patterning of the embryo. Here, we reveal an unexpected role for Semaphorin-2a (Sema2a) in actin mesh regulation and oogenesis. Sema2a classically functions as a secreted guidance cue that binds its cognate Plexin-B (PlexB) receptor to establish neural circuits. In contrast, we find that Sema2a is expressed inside the germarium, germline, and follicle cells of the developing ovary. Sema2a mutants possess small ovaries that fail to develop past mid-oogenesis. We demonstrate that Sema2a interacts with Cappuccino (Capu), a key actin nucleator crucial for building the actin mesh in Drosophila oocytes. Sema2a inhibits the actin assembly activity of Capu in vitro. Furthermore, genetic interaction between Sema2a and Capu influences mesh density and disrupts oskar mRNA localization. PlexB mutants, however, exhibit wild-type size ovaries with oskar mRNA localization distinct from Sema2a mutants, confirming the non-canonical role of Sema2a in oogenesis.

  PublisherDOI

• Nascent dendrite branches initiated by a localized burst of Spire-dependent actin polymerization

  Development · 2025-09-12

  articleOpen access

  Dendrites form arbors whose size, shape and complexity define how neurons cover their receptive territories. Actin dynamics contribute to growth and remodeling of dendrite arbors. Here, we have examined how Spire, a conserved actin nucleation factor, promotes the formation of new branches in vivo. In live imaging of Drosophila class IV dendritic arborization (c4da) neurons, Spire was observed at new sites of branch initiation, where it assembled new actin polymer in a burst immediately before filopodial outgrowth. For dendrite arborization, Spire required intact structural domains to nucleate actin and target the secretory network, and interacted with Rab11 GTPase, a key regulator of recycling endosomes. Together, these findings support a model in which Spire cooperates with Rab11 to promote new dendrite branches by linking localized actin dynamics with intracellular trafficking of endosomes that deliver lipids and cargoes to fuel protrusive outgrowth of nascent dendrites.

  PublisherOA PDFDOI

• Human formin FHOD3-mediated actin elongation is required for sarcomere integrity in cardiomyocytes

  eLife · 2025-07-15

  articleOpen accessSenior author

  Contractility and cell motility depend on accurately controlled assembly of the actin cytoskeleton. Formins are a large group of actin assembly proteins that nucleate and elongate new actin filaments. Some formins may cap filaments while others sever or bundle filaments. The formin homology domain-containing protein (FHOD) family of formins is critical to the formation of the fundamental contractile unit in muscle, the sarcomere. Specifically, mammalian FHOD3L plays an essential role in cardiomyocytes. Despite our knowledge of FHOD3L’s importance in cardiomyocytes, its biochemical and cellular activities remain poorly understood. It was proposed that FHOD-family formins act by capping and bundling, as opposed to assembling new filaments. Here, we demonstrate that human FHOD3L nucleates actin and rapidly but briefly elongates filaments after temporarily pausing elongation. We designed function-separating mutants that enabled us to distinguish which biochemical roles are required in the cell. We found that FHOD3L’s elongation activity, but not its nucleation, capping, or bundling activity, is necessary for proper sarcomere formation and contractile function in neonatal rat ventricular myocytes. The results of this work provide new insight into the mechanisms by which formins build specific structures and will contribute to knowledge regarding how cardiomyopathies arise from defects in sarcomere formation and maintenance.

  PublisherDOI

• Human formin FHOD3-mediated actin elongation is required for sarcomere integrity in cardiomyocytes

  eLife · 2025-06-18

  preprintOpen accessSenior author

  Abstract Contractility and cell motility depend on accurately controlled assembly of the actin cytoskeleton. Formins are a large group of actin assembly proteins that nucleate and elongate new actin filaments. Some formins may cap filaments while others sever or bundle filaments. The Formin HOmology Domain-containing protein (FHOD)-family of formins is critical to the formation of the fundamental contractile unit in muscle, the sarcomere. Specifically, mammalian FHOD3L plays an essential role in cardiomyocytes. Despite our knowledge of FHOD3L’s importance in cardiomyocytes, its biochemical and cellular activities remain poorly understood. It was proposed that FHOD-family formins act by capping and bundling, as opposed to assembling new filaments. Here, we demonstrate that FHOD3L nucleates actin and rapidly but briefly elongates filaments after temporarily pausing elongation. We designed function-separating mutants that enabled us to distinguish which biochemical roles are required in the cell. We found that human FHOD3L’s elongation activity, but not its nucleation, capping, or bundling activity, is necessary for proper sarcomere formation and contractile function in neonatal rat ventricular myocytes. The results of this work provide new insight into the mechanisms by which formins build specific structures and will contribute to knowledge regarding how cardiomyopathies arise from defects in sarcomere formation and maintenance.

  PublisherDOI

• Author response: Human formin FHOD3-mediated actin elongation is required for sarcomere integrity in cardiomyocytes

  2025-06-18

  peer-reviewOpen accessSenior author

  Contractility and cell motility depend on accurately controlled assembly of the actin cytoskeleton. Formins are a large group of actin assembly proteins that nucleate and elongate new actin filaments. Some formins may cap filaments while others sever or bundle filaments. The Formin HOmology Domain-containing protein (FHOD)-family of formins is critical to the formation of the fundamental contractile unit in muscle, the sarcomere. Specifically, mammalian FHOD3L plays an essential role in cardiomyocytes. Despite our knowledge of FHOD3L’s importance in cardiomyocytes, its biochemical and cellular activities remain poorly understood. It was proposed that FHOD-family formins act by capping and bundling, as opposed to assembling new filaments. Here, we demonstrate that FHOD3L nucleates actin and rapidly but briefly elongates filaments after temporarily pausing elongation. We designed function-separating mutants that enabled us to distinguish which biochemical roles are required in the cell. We found that human FHOD3L’s elongation activity, but not its nucleation, capping, or bundling activity, is necessary for proper sarcomere formation and contractile function in neonatal rat ventricular myocytes. The results of this work provide new insight into the mechanisms by which formins build specific structures and will contribute to knowledge regarding how cardiomyopathies arise from defects in sarcomere formation and maintenance.

  PublisherDOI

• Author response: Human formin FHOD3-mediated actin elongation is required for sarcomere integrity in cardiomyocytes

  2025-07-15

  peer-reviewOpen accessSenior author
  PublisherDOI

• The Influence of <i>Drosophila</i> Spire and Myosin V During Mid‐Oogenesis Is Independent of Their Direct Interaction

  Cytoskeleton · 2025-12-08

  articleOpen accessSenior authorCorresponding

  Cooperativity between cytoskeletal proteins is crucial for spatiotemporal coordination in biological processes, like oogenesis. In mammalian and Drosophila oogenesis, proper assembly and function of actin networks require coordination between actin assembly factors Spire and formins, as well as actin-associated proteins like myosins and Rab GTPases. Here, we investigate the interaction between Spire and Myosin V (MyoV) in Drosophila oogenesis. We combine in vitro biochemical assays with immunofluorescence and genetics to probe the interaction and its impact on polarity establishment and the actin mesh that fills the oocyte during mid-oogenesis. Expressed Spire and MyoV constructs colocalize in punctae during mid oogenesis, with considerable enrichment near the oocyte cortex. Purified constructs interact directly in vitro, and we find that Spire can weakly activate MyoV ATPase activity. Cytoplasmic flows, critical for polarity establishment, are faster and more coordinated in the absence of MyoV, although not to the extent of fast streaming. This intermediate streaming has not been observed before. Interestingly, this MyoV-dependent change in ooplasm dynamics is sensitive to Spire levels. Despite this interplay, the actin mesh and polarity establishment appear normal when binding mutants of Spire and MyoV are expressed in the Drosophila germline. These findings suggest that direct interaction between Spire and MyoV is not essential for their primary roles at this stage of development.

  PublisherOA PDFDOI

• Impact of N-terminal dimerization on formin homology 1 domain polymer dynamics and actin assembly

  Biophysical Journal · 2025-11-23

  articleOpen access

  Abstract Many proteins contain intrinsically disordered regions (IDRs) that lack stable 3-dimensional structure. IDR behavior is poorly understood, leading to challenges for biochemical and computational analysis of IDR-containing proteins. Formins are a diverse set of homodimers containing an IDR — the FH1 domain — that facilitates polymerization of the cytoskeletal protein actin by increasing the local concentration of actin monomers at the actin assembly site. A commonly accepted model of formin-based actin polymerization involves a capture-and-deliver process: one or more binding sites (proline-rich motifs, PRMs) “capture” actin monomers and then “deliver” actin to the actin assembly site. There is evidence that formin FH1 domains are dimerized on both ends, but much research has been performed with formin constructs lacking the N-terminal dimerization site. Here, we ask: What happens when N-terminal dimerization is added to the standard model of formin-mediated actin assembly? We extend the kinetic model of FH1-mediated actin polymerization by incorporating a coarse-grain polymer model of FH1 domain dynamics, modeling the FH1 domain as a freely-jointed chain. We find that N-terminal dimerization can impact polymerization rates by modifying binding site accessibility and/or local concentration of binding sites (PRMs) at the actin assembly site (FH2 domain). Which effect dominates depends on kinetic parameters and formin properties such as FH1 domain length and binding site location. Additionally, we demonstrate that our model can be fit to experimental data and used to make predictions for the effects of N-terminal dimerization on a variety of formin family members. Significance Intrinsically disordered regions (IDRs) are common protein components that lack stable 3D structures and are thus difficult to study. Here, we develop a polymer-physics based computational model of the formin FH1 domain, an IDR involved in building the cell’s cytoskeleton. Some disease-associated mutations of formins occur in a region that is suspected to induce dimerization, forcing the FH1 domains to form a loop. Little is known about the loop’s prevalence, location, or impact on cytoskeletal assembly. Using simple polymer physics, we demonstrate that this dimerization can alter FH1 domain polymer dynamics and thus impact cytoskeletal assembly. These results not only highlight an important aspect of FH1-mediated cytoskeletal assembly, but also provide a framework for modeling IDRs.

  PublisherDOI

• Author response: Human formin FHOD3-mediated actin elongation is required for sarcomere integrity in cardiomyocytes

  2024-12-20

  peer-reviewOpen accessSenior author

  Contractility and cell motility depend on accurately controlled assembly of the actin cytoskeleton. Formins are a large group of actin assembly proteins that nucleate new actin filaments and act as elongation factors. Some formins may cap filaments, instead of elongating them, and others are known to sever or bundle filaments. The Formin HOmology Domain-containing protein (FHOD)-family of formins is critical to the formation of the fundamental contractile unit in muscle, the sarcomere. Specifically, mammalian FHOD3L plays an essential role in cardiomyocytes. Despite our knowledge of FHOD3L’s importance in cardiomyocytes, its biochemical and cellular activities remain poorly understood. It has been proposed that FHOD-family formins act by capping and bundling, as opposed to assembling new filaments. Here, we demonstrate that FHOD3L nucleates actin and rapidly but briefly elongates filaments after temporarily pausing elongation, in vitro. We designed function-separating mutants that enabled us to distinguish which biochemical roles are req՝uired in the cell. We found that human FHOD3L’s elongation activity, but not its nucleation, capping, or bundling activity, is necessary for proper sarcomere formation and contractile function in neonatal rat ventricular myocytes. The results of this work provide new insight into the mechanisms by which formins build specific structures and will contribute to knowledge regarding how cardiomyopathies arise from defects in sarcomere formation and maintenance.

  PublisherDOI

• Human formin FHOD3-mediated actin elongation is required for sarcomere integrity in cardiomyocytes

  eLife · 2024-12-20

  preprintOpen accessSenior author

  Abstract Contractility and cell motility depend on accurately controlled assembly of the actin cytoskeleton. Formins are a large group of actin assembly proteins that nucleate new actin filaments and act as elongation factors. Some formins may cap filaments, instead of elongating them, and others are known to sever or bundle filaments. The Formin HOmology Domain-containing protein (FHOD)-family of formins is critical to the formation of the fundamental contractile unit in muscle, the sarcomere. Specifically, mammalian FHOD3L plays an essential role in cardiomyocytes. Despite our knowledge of FHOD3L’s importance in cardiomyocytes, its biochemical and cellular activities remain poorly understood. It has been proposed that FHOD-family formins act by capping and bundling, as opposed to assembling new filaments. Here, we demonstrate that FHOD3L nucleates actin and rapidly but briefly elongates filaments after temporarily pausing elongation, in vitro. We designed function-separating mutants that enabled us to distinguish which biochemical roles are req՝uired in the cell. We found that human FHOD3L’s elongation activity, but not its nucleation, capping, or bundling activity, is necessary for proper sarcomere formation and contractile function in neonatal rat ventricular myocytes. The results of this work provide new insight into the mechanisms by which formins build specific structures and will contribute to knowledge regarding how cardiomyopathies arise from defects in sarcomere formation and maintenance.

  PublisherDOI

Recent grants

• Collaboration between actin nucleators - Spire and Cappuccino

  NIH · $4.1M · 2011–2025

Frequent coauthors

• Yale E. Goldman

  16 shared

• Joseph N. Forkey

  16 shared

• Christina L. Vizcarra

  Barnard College

  11 shared

• Dylan A Valencia

  The University of Texas at Austin

  9 shared

• Yujie Sun

  Peking University

  8 shared

• John F. Beausang

  Menlo School

  8 shared

• Zeynep A. Oztug Durer

  Kent Hastanesi

  6 shared

• Haruko Nakano

  University of California, Los Angeles

  5 shared

Education

• Ph.D., Cell and Molecular Biology

  University of Pennsylvania

  2002

• BA, Biology

  Reed College

  1991

Awards & honors

• Hanson-Dow Excellence in Teaching Award, Department of Chemi…
• Undergraduate Research Week Faculty Mentor Award, UCLA Under…
• Faculty Fellows, UCLA Center for Diverse Leadership in Scien…
• Academic Leadership Training Workshop – 1 of 38 national app…
• Faculty Career Development Award, UCLA, 2014