The role of microtubule-associated proteins in the generation and regulation of spindle shape

doctoral thesis

• Title (croatian): Uloga proteina vezanih na mikrotubule u stvaranju i regulaciji oblika diobenoga vretena
• Author: Monika Trupinić
• Mentor: Iva Marija Tolić (mentor)
• Committee member: Dragomira Majhen (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-06-13, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 576 - Cellular and subcellular biology. Cytology

Abstract

In the mitotic spindle, a complex micro-structure responsible for the segregation of chromosomes,
individual microtubule bundles obtain different shapes depending on the mechanical forces acting
on them. In addition to linear forces, rotational forces are present in the spindle, reflected in the
left-handed twisted shapes of microtubule bundles that make the spindle chiral. However, it is not
known how twist changes throughout mitosis in non-tumor cells, or what are the molecular origins
of the twist. This doctoral thesis shows that twist in non-tumor cells is most pronounced at the start
of the anaphase, and can be affected by manipulating microtubule-associated proteins, such as
motor proteins, but also proteins that crosslink or nucleate microtubule bundles. It also explores
how spindles react to the external forces by widening or increasing the twist. To conclude, this
thesis uncovers how bending and twisting moments are generated by similar molecular
mechanisms and it proposes a physiological role for spindle chirality in allowing the spindle to
absorb mechanical load.

Abstract (croatian)

Unutar diobenog vretena, složene mikro-strukture odgovorne za podijelu kromosoma, pojedinačni
svežnjevi mikrotubula poprimaju različite oblike pod djelovanjem mehaničkih sila. U vretenu,
osim linearnih sila, prisutne su i rotacijske sile koje se očituju kroz lijevo usmjereni zaokret
svežnjeva mikrotubula što čini diobeno vreteno kiralnim. Međutim, nije poznato kako se takav
zaokret mijenja kroz različite faze mitoze u netumorskim stanicama, niti koje su njegove
molekularne osnove. U ovom doktorskom radu prikazano je kako je zaokret vretena najizraženiji
na početku anafaze te podložan promjenama nakon manipulacije proteina vezanih na mikrotubule,
kao što su motorni proteini, ali i proteini koji unakrsno vežu mikrotubule ili stvaraju nove. Također,
prikazano je kako vretena reagiraju na pritisak vanjskih sila širenjem ili povećanjem zaokreta. Kao
zaključak, ova teza prikazuje kako su slični molekularni mehanizmki odgovorni za stvaranje
savijanja i zakretanja vretena te predlaže fiziolšku ulogu kiralnosti u očuvanju vretena nakon
djelovanja mehaničkih sila.

• Keywords: mitotic spindle; chirality; twist; motor proteins; augmin; PRC1; spindle compression
• Keywords (croatian): diobeno vreteno; kiralnost; zaokret; motorni proteini; augmin; PRC1; stiskanje
• Language: english
• URN:NBN: urn:nbn:hr:217:734850
• Promotion: 2023
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-07-12 11:10:03