Margaret Robinson

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Margaret Robinson
FRS FMedSci
Born (1951-12-29) 29 December 1951 (age 72) [1]
Alma mater
Known for Adaptins
Scientific career
Fieldscell biology
Institutions MRC Laboratory of Molecular Biology
University of Cambridge
Thesis Endocytosis in granulosa cells  (1982)
Doctoral advisor Barbara Pearse
Website www.cimr.cam.ac.uk/staff/professor-margaret-robinson-frs

Margaret Scott Robinson (born 1951) [1] FRS FMedSci is a British molecular cell biologist, a professor and researcher in the Cambridge Institute for Medical Research, at the University of Cambridge. [2]

Contents

Education

Robinson received her Bachelor of Arts degree in biology from Smith College in Massachusetts. [3] She completed her PhD at Harvard University supervised by David Albertini and also Barbara Pearse. [4] [5] In 2003 she was appointed Professor of Molecular Cell Biology at the Cambridge Institute for Medical Research [6] and is conducting research on coated vesicle proteins. [3]

Margaret Robinson was first exposed about science early in her life from reading about Marie Curie. While enrolled at Smith College, she planned on being an English or theater major. However, due to university requirements, Margaret had to complete an introductory biology course. In that course, Jeanne Powell gave a lecture on cells and showed her students electron micrographs. [5] This is when Margaret really became interested in cellular biology; the complexity of cells intrigued her.

After receiving her undergraduate degree, Robinson took a year off and ended up at Harvard Medical School. [5]

Robinson eventually joined a new lab and was able to conduct research on anything she liked. Due to her inexperience, her research did not go as planned and was nearly kicked out of graduate school. [5] Robinson had to stop working on her interest in coated vesicles and work on something closer to what the lab was researching.

Robinson eventually started a postdoctoral research with Barbara Pearse, [5] joining her at the MRC Laboratory of Molecular Biology in December 1982. [7] Her interest was in clathrin-coated vesicles that binds to cargo. She eventually succeeded in purifying components of the coat that were not clathrin and are now known as adaptor proteins. [5] These proteins sit between clathrin, which forms the vesicle's outer shell and also the vesicle membrane. Continuing, Margaret discovered that there were two different populations of clathrin-coated vesicles, one that uses AP-2 at the plasma membrane and one that uses AP-1 and was associated with intracellular membranes. [5] AP-1 and AP-2 are both heterotetramers with related subunits. They both have two large subunits and the other subunit is closely related in AP-1 and AP-2.

Research

Her achievements include the discovery of adaptins, which are specific proteins that manage cell-trafficking to ensure the correct cell cargo is transported to the right location. [2] She also discovered different combinations of adapting, when together with clathrin, form a coat around vesicles that bud from intracellular membranes and act as transporters for protein packages to be distributed in the cell. She also developed the technique “knock sideways,” which inactivates proteins in seconds. [8]

After finishing her postdoc, she was able to start her own lab. Her main focus was to learn more about the AP protein in depth. [5] She had to also work with DNA because in order to characterize the complexes thoroughly, she needed to clone the subunits. Robinson and her lab managed to find another AP complex, AP-3, which interacts with lysosomal membrane proteins such as LAMP1. [5] AP-3 also interacts with tyrosinase, which is a key enzyme in melanin biosynthesis, so AP-3 is important for tyrosinase trafficking to premelanosomes. [5]

As of 2016 Robinson has a lab at Cambridge Institute for Medical Research. [8] She specifically works with coated vesicles. The best-characterized coated vesicles are the clathrin-coated vesicles (CCVs). The coats on CCVs are primarily of clathrin, adaptor protein (AP) complexes, and alternative adaptors. Her working hypothesis is that for each trafficking pathway, there are a number of different adaptors, each of which is recruited independently onto the appropriate membrane. [8] Once on the membrane, the various adaptors would work together to package different types of cargo into the newly forming vesicle. Robinson and her researchers use several approaches to look for novel adaptors and other components of the trafficking machinery, including proteomic analyses of sub cellular fractions, genome-wide siRNA library screening, insertional mutagenesis, and a new method they developed for rapidly inactivating proteins, called ‘knock sideways’. [2] Her current projects include establishing the functions of AP-1 and other adaptors in differentiated cells; matching up machinery and cargo proteins; investigating how clathrin and adaptors are hijacked by the HIV-1-encoded protein Nef; determine why mutations in the non-clathrin adaptors AP-4 and AP-5 cause hereditary spastic paraplegia; and exploring the evolution of adaptors. [9] Her laboratory uses many techniques including immunolocalisation at the light and electron microscope levels, sub cellular fractionation, protein purification, proteomics, flow cytometry, live cell imaging, and X-ray crystallography.

Impact of research

Every form of eukaryotic life on earth contains coated vesicles and adaptors. Her work is also speculated to play a key role in evolution of eukaryotes form prokaryotes over two billion years ago. Her work also has medical implications. Some adaptors are mutated in certain genetic disorders, and adaptors are frequently exploited by pathogens . For example, the HIV genome encodes a protein called Nef, which is required for the development of AIDS, and which works by hijacking adaptors and using them to modify the surface of the infected cell.

Robinson's work explains how coated vesicles sort cargo but also provides tools that can be used by others to address their own favorite problems. For instance, her newly developed method called knocksideways. Knocksideways gets rid of proteins rapidly. Her technique has found its way into other labs who are also interested in how particular proteins contribute to different stages of cell division. [9]

Selected publications

Awards and honours

Robinson has received many honors working as a cellular biologist. She was awarded a Wellcome Trust Principal Research Fellowship in 1999 and in 2003 she was appointed Professor of Molecular Cell Biology. [3] She was elected a Fellow of the Academy of Medical Sciences [ when? ] and member of the European Molecular Biology Organization.[ when? ] She was elected a Fellow of the Royal Society (FRS) in 2012. [2] The Wellcome Trust also has funded her research for over 25 years. [9]

Related Research Articles

<span class="mw-page-title-main">Endocytosis</span> Cellular process

Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested materials. Endocytosis includes pinocytosis and phagocytosis. It is a form of active transport.

<span class="mw-page-title-main">Clathrin</span> Protein playing a major role in the formation of coated vesicles

Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice that surrounds the vesicle. The protein's name refers to this lattice structure, deriving from Latin clathri meaning lattice. Barbara Pearse named the protein clathrin at the suggestion of Graeme Mitchison, selecting it from three possible options. Coat-proteins, like clathrin, are used to build small vesicles in order to transport molecules within cells. The endocytosis and exocytosis of vesicles allows cells to communicate, to transfer nutrients, to import signaling receptors, to mediate an immune response after sampling the extracellular world, and to clean up the cell debris left by tissue inflammation. The endocytic pathway can be hijacked by viruses and other pathogens in order to gain entry to the cell during infection.

<span class="mw-page-title-main">COPI</span> Protein complex

COPI is a coatomer, a protein complex that coats vesicles transporting proteins from the cis end of the Golgi complex back to the rough endoplasmic reticulum (ER), where they were originally synthesized, and between Golgi compartments. This type of transport is retrograde transport, in contrast to the anterograde transport associated with the COPII protein. The name "COPI" refers to the specific coat protein complex that initiates the budding process on the cis-Golgi membrane. The coat consists of large protein subcomplexes that are made of seven different protein subunits, namely α, β, β', γ, δ, ε and ζ.

<span class="mw-page-title-main">Receptor-mediated endocytosis</span> Process by which cells absorb materials

Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, proteins – and in some cases viruses – by the inward budding of the plasma membrane (invagination). This process forms vesicles containing the absorbed substances and is strictly mediated by receptors on the surface of the cell. Only the receptor-specific substances can enter the cell through this process.

<span class="mw-page-title-main">Vesicular transport adaptor protein</span>

Vesicular transport adaptor proteins are proteins involved in forming complexes that function in the trafficking of molecules from one subcellular location to another. These complexes concentrate the correct cargo molecules in vesicles that bud or extrude off of one organelle and travel to another location, where the cargo is delivered. While some of the details of how these adaptor proteins achieve their trafficking specificity has been worked out, there is still much to be learned.

Barbara Mary Frances Pearse FRS is a British biological scientist. She works at the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom.

<span class="mw-page-title-main">AP2 adaptor complex</span>

The AP2 adaptor complex is a multimeric protein that works on the cell membrane to internalize cargo in clathrin-mediated endocytosis. It is a stable complex of four adaptins which give rise to a structure that has a core domain and two appendage domains attached to the core domain by polypeptide linkers. These appendage domains are sometimes called 'ears'. The core domain binds to the membrane and to cargo destined for internalisation. The alpha and beta appendage domains bind to accessory proteins and to clathrin. Their interactions allow the temporal and spatial regulation of the assembly of clathrin-coated vesicles and their endocytosis.

<span class="mw-page-title-main">AP2M1</span> Protein-coding gene in the species Homo sapiens

AP-2 complex subunit mu is a protein that in humans is encoded by the AP2M1 gene.

<span class="mw-page-title-main">AP1M1</span> Protein-coding gene in the species Homo sapiens

AP-1 complex subunit mu-1 is a protein that in humans is encoded by the AP1M1 gene.

<span class="mw-page-title-main">AP1G1</span> Protein-coding gene in the species Homo sapiens

AP-1 complex subunit gamma-1 is a protein that in humans is encoded by the AP1G1 gene.

<span class="mw-page-title-main">AP1B1</span> Protein-coding gene in the species Homo sapiens

AP-1 complex subunit beta-1 is a protein that in humans is encoded by the AP1B1 gene.

<span class="mw-page-title-main">AP2B1</span> Protein-coding gene in the species Homo sapiens

AP-2 complex subunit beta is a protein that in humans is encoded by the AP2B1 gene.

<span class="mw-page-title-main">AP3D1</span> Protein-coding gene in the species Homo sapiens

AP-3 complex subunit delta-1 is a protein that in humans is encoded by the AP3D1 gene.

<span class="mw-page-title-main">AP1M2</span> Protein-coding gene in the species Homo sapiens

AP-1 complex subunit mu-2 is a protein that in humans is encoded by the AP1M2 gene.

<span class="mw-page-title-main">AP1S1</span> Protein-coding gene in the species Homo sapiens

AP-1 complex subunit sigma-1A is a protein that in humans is encoded by the AP1S1 gene.

<span class="mw-page-title-main">AAK1</span> Protein-coding gene in the species Homo sapiens

Adaptor-associated protein kinase 1 also known as AP2-associated protein kinase 1 is an enzyme that in humans is encoded by the AAK1 gene and is involved in clathrin mediated endocytosis. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Clathrin adaptor proteins, also known as adaptins, are vesicular transport adaptor proteins associated with clathrin. These proteins are synthesized in the ribosomes, processed in the endoplasmic reticulum and transported from the Golgi apparatus to the trans-Golgi network, and from there via small carrier vesicles to their final destination compartment. The association between adaptins and clathrin are important for vesicular cargo selection and transporting. Clathrin coats contain both clathrin and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Therefore, adaptor proteins are responsible for the recruitment of cargo molecules into a growing clathrin-coated pits. The two major types of clathrin adaptor complexes are the heterotetrameric vesicular transport adaptor proteins (AP1-5), and the monomeric GGA adaptors. Adaptins are distantly related to the other main type of vesicular transport proteins, the coatomer subunits, sharing between 16% and 26% of their amino acid sequence.

<span class="mw-page-title-main">Beta2-adaptin C-terminal domain</span>

The C-terminal domain ofBeta2-adaptin is a protein domain is involved in cell trafficking by aiding import and export of substances in and out of the cell.

<span class="mw-page-title-main">Muniscins</span>

The muniscin protein family was initially defined in 2009 as proteins having 2 homologous domains that are involved in clathrin mediated endocytosis (CME) and have been reviewed. In addition to FCHO1, FCHO2 and Syp1, SGIP1 is also included in the family because it contains the μ (mu) homology domain and is involved in CME, even though it does not contain the F-BAR domain

References

  1. 1 2 "ROBINSON, Prof. Margaret Scott" . Who's Who . Vol. 2016 (online Oxford University Press  ed.). Oxford: A & C Black.(Subscription or UK public library membership required.)
  2. 1 2 3 4 "Margaret Robinson". London: Royal Society.
  3. 1 2 3 "Margaret Robinson". rnaiglobal.org.
  4. ↑ Robinson, Margaret Scott (1982). Endocytosis in granulosa cells (PhD thesis). Harvard University. OCLC   9791498.
  5. 1 2 3 4 5 6 7 8 9 10 Sedwick, Caitlin (2014). "Margaret Robinson: Vesicles wear fancy coats". The Journal of Cell Biology. 206 (6): 692–693. doi:10.1083/jcb.2066pi. PMC   4164944 . PMID   25225335.
  6. ↑ "Professor Margaret Scott Robinson elected to the Fellowship of the Royal Society". cam.ac.uk. 26 April 2012. Retrieved 27 October 2016.
  7. ↑ Weston, Kathleen (2020). Stannard, Dorothy (ed.). Ahead of the Curve: Women Scientists at the MRC Laboratory of Molecular Biology. Cambridge, UK: MRC Laboratory of Molecular Biology. p. 107. ISBN   978-1-903435-05-2.
  8. 1 2 3 "Margaret Robinson: Cambridge Institute for Medical Research". Cambridge: cam.ac.uk.
  9. 1 2 3 "Researcher Spotlight: Margaret Robinson". London: Wellcome Trust. 13 September 2023.
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